BEHAVIOR GENETICS ASSOCIATION
31st ANNUAL MEETING
PETERHOUSE COLLEGE, CAMBRIDGE, ENGLAND
July 8 -11, 2001

The purpose of the Behavior Genetics Association is to promote scientific study of the interrelationship of genetic mechanisms and behavior, both human and animal; to encourage and aid the education and training of research workers in the field of behavior genetics; and to aid in the dissemination and interpretation to the general public of knowledge concerning the interrelationship of genetics and behavior, and its implications for health and human development and education.

For additional information about the Behavior Genetics Association, please contact Dr. Hermine Maes BGA Secretary, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Box 980003, Richmond VA 23298

EXECUTIVE COMMITTEE 2000-2001 2001-2002
President
President-Elect
Past President
Secretary
Treasurer
Member-at-Large
Member-at-Large
Member-at-Large
John Hewitt
Matt McGue
Richard Rose
Hermine Maes
Pam Madden
Irwin Waldman
Jennifer Harris
Carol Prescott
Matt McGue
Nancy Pedersen
John Hewitt
Michael Pogue-Geile
Pam Madden
Jennifer Harris
Carol Prescott
Caroline Van Baal

MEETING INFORMATION

The 31st Annual Meeting of the Behavior Genetics Association will be held at Peterhouse College, a college of the University of Cambridge. Paper, poster and plenary sessions will be held throughout the day on the 9th, 10th and 11th of July. The opening reception is scheduled to begin at 6:00 PM on Sunday July the 8th. The banquet will be held on Wednesday the 11th.

Peterhouse College Situated in the heart of picturesque Cambridge, beside the peaceful river Cam, Peterhouse College was founded in 1284 and its Hall, constructed between 1286 and 1290, was the first collegiate building in Cambridge. The variety and charm of its interior derive from the 19th century stained glass, wall tiles and decoration by William Morris, Edward Burne-Jones and Ford Maddox-Brown. The college theatre, where the majority of the conference will be held, with its curving auditorium and gallery was converted from a Victorian lecture room. Cambridge itself needs no introduction. One of England's most elegant and historical town centre is only a short stroll away from the conference venue.

Sanger Centre This genome research centre was set up in 1992 by the Wellcome Trust and the Medical Research Council in order to further our knowledge of genomes, and in particular to play a substantial role in the sequencing and interpretation of the human genome. The Centre is situated on the Wellcome Trust genome Campus at Hinxton Hall, a 55-acre parkland site 15 minutes south of the university city of Cambridge. More information on the Centre can be obtained from the website: www.sanger.ac.uk. The visit will include a tour of the laboratories followed by a brief talk and discussion session.

Local Host: Dr. Thalia Eley
SGDP Research Centre
Institute of Psychiatry
111 Denmark Hill
London SE5 8AF UK
Tel: +44 (0) 20 7848 0863
Fax: +44(0) 20 7848 0866
Email: t.eley@iop.kcl.ac.uk

Year Presidents Dobzhansky Awardees Thompson Awardees Local Hosts
1971 R Osborne/B Ginsburg - Storrs CT
1972 Th. Dobzhansky GE McClearn - Boulder CO
1973 John L. Fuller WS Pollitzer - Chapel Hill NC
1974 Gerald E. McClearn S Scarr - Minneapolis MN
1975 J. P. Scott J Bruell - Austin TX
1976 Irving I. Gottesman JC DeFries - Boulder CO
1977 W. R. Thompson Steven Vandenberg Nancy Galvin R Wilson - Louisville KY
1978 Lee Ehrman Elliott Slater Gregory Carey T Klein - Davis CA
1979 V. Elving Anderson Ernst Caspari Marla Sokolowski C Lynch - Middletown CT
1980 John C. Loehlin Benson Ginsburg RD Bock - Chicago IL
1981 Norman D. Henderson Sheldon Reed Michael Pogue-Geile L Erhman - Purchase NY
Rose/Guttman/Guttman - Jerusalem
1982 John C. DeFries Gardner Lindzey Paul Sharp D Nash - Ft Collins CO
1983 David W. Fulker Peter Broadhurst Michael Neale D Fulker - London
1984 Steven G. Vandenberg Leonard Heston Christine Michard & George Vogler R Rose - Bloomington IN
1985 Sandra Scarr Nikki Erlenmeyer-Kimling Dorret Boomsma & Lucinda Miner G McClearn - State College PA
1986 Ronald S. W ilson Raymond Cattell David Harder G Ashton/R Johnson - Honolulu HI
1987 Peter A. Parsons J L Fuller & J P Scott J. S. de Belle L Heston - Minneapolis
1988 Leonard L. Heston Lee Erhman Joanne Meyer S Kerbusch - Nijmegen, Netherl.
1989 Robert Plomin Gerald McClearn Susan Parlour S Scarr - Charlottesville VA
1990 Carol B. Lynch Irving Gottesman Lon Cardon & Philip Welbergen P Roubertoux - Aussois, France
1991 Lindon J. Eaves John Loehlin Abel Bult & Lawrence Rodriguez G Vogler - St Louis MO
1992 David A. Blizard John DeFries Deborah Finkel J Wilson - Boulder CO
1993 Thomas J. Bouchard, Jr.Peter Parsons Hermine Maes N Martin - Sydney, Australia
1994 Glayde Whitney Aubrey Manning Frans Sluyter A Fernandez-Teruel/RM Escorihuela/A Tobena - Barcelona
1995 James Wilson David Fulker Soo HyunRhee & Stephen PetrillJ Meyer/L Eaves -Richmond
1996 Nicholas Martin Stephanie Schmitz G McClearn/G Vogler/D Blizard/B Jones - Pittsburgh PA
1997 Nicholas Martin Ronald Johnson Martine Thomis Tony Vernon -Toronto, Canada
1998 Norman Henderson Stephen Maxson Javier Gayán & Alexander Weiss N Pedersen - Stockholm, Sweden
1999 Richard Rose Lindon Eaves Danielle Posthuma & Danielle Dick Kerry Jang, Vancouver, Canada
2000John Hewitt Pierre Roubertoux Brian D'Onofrio & Nathan Gillespie James Hudziak, Burlington, Vermont

BEHAVIOR GENETICS ASSOCIATION
31st ANNUAL MEETING
Peterhouse College, Cambridge, England
July 8-11, 2001
SUNDAY JULY 8
2:00 - 6:00 REGISTRATION
4:00 - 5:00 EXECUTIVE COMMITTEE MEETING
6:00 - 8:00 WELCOME RECEPTION
MONDAY JULY 9
Monday July 9th
9:00 - 11:00
PAPER SESSION I
Cognitive Ability
Chair: Michael F. Pogue-Geile
9:00 - 9:15 Functional analysis of genes included in the Down syndrome chromosomal region-1 (DCR-1) with transpolygenic mice
Caroline Chabert, Ameziane Cherfouh, Vincent Duquenne and Pierre L. Roubertoux
9:15 - 9:30 General Cognitive Ability (g) in Mice as the basis of a Functional Genomics Model of Cognitive Abilities and Disabilities
Michael J. Galsworthy, Jose L. Paya-Cano, Lin Liu, Santiago Monleon and Robert Plomin
9:30 - 9:45 Modularity and genetic correlation in cognitive development: A study of pre-school age twins (T)
Tom S. Price, P.S. Dale, T.C. Eley and Robert Plomin
9:45 - 10:00 Genetics of electroencephalographic coherence and intelligence in young twins
G. Caroline M. van Baal, Dorret I. Boomsma and Eco J.C. de Geus
10:00 - 10:15 Socioeconomic status modifies heritability of intelligence in impoverished children
Eric Turkheimer, Andreana Haley, Brian D'Onofrio, Mary Waldron, Robert E. Emery and Irving I. Gottesman
10:15 - 10:30 Cognitive Function and Dopamine Transporter (DAT) Genetic Polymorphisms: A Twin and Genetic Association Study
Michael F. Pogue-Geile, Stephen Manuck, Robert Ferrell and Thomas Debski
10:30 - 10:45 Are faster brains also smarter? (T)
Danielle Posthuma, Dorret I. Boomsma, G. Caroline C. van Baal and Eco J.C. de Geus
10:45 - 11:00 Association between APOE and ACE genotypes and cognitive decline
Chandra A. Reynolds, Lars Feuk, Margaret Gatz, Ulf de Faire, Anthony Brookes and Nancy L. Pedersen
Monday July 9th
9:00 - 11:00
PAPER SESSION II
Childhood Psychopathology and Neurological Disorder
Chair: Maricela Alarcón
9:00 - 9:15 Genetic analysis of DSM-oriented scales in 3 year-old Dutch twins
Dorret Boomsma, Toos van Beijsterveldt, Caroline van Baal, Therese Stroet, Tinca Polderman, Alexia Groot, Jolande van der Valk, Frank Verhulst, Tom Achenbach and Jim Hudziak
9:15 - 9:30 Daytime Basal Cortisol and Common Childhood Psychopathology
Meike Bartels, E.J.C. de Geus, C. Kirschbaum, M.J.H. Rietveld and D.I. Boomsma
9:30 - 9:45 Shared environmental effects are important for stability and genetic effects for change in fears and phobias in the transition from childhood to early adolescence
Paul Lichtenstein and Peter Annas
9:45 - 10:00 Neonatal seizures, M-channels, and retigabine
V. Elving Anderson
10:00 - 10:15 Linkage Analysis of Language Traits in Autistic Families
Maricela Alarcón, Rita M. Cantor, AGRE Consortium and Daniel H. Geschwind
10:15 - 10:30 Intergenerational Transmission of ADHD and Associated Psychopathologies
Florence Levy, David A. Hay, Michael McStephen and Nicholas G. Martin
10:30 - 10:45 Modelling the relationship of Inattention and Hyperactivity/Impulsivity in ADHD
Michael McStephen, David A. Hay and Florence Levy
10:45 - 11:00
11:00 - 11:30 TEA
Monday July 9th
11:30 - 12:30
PLENARY ADDRESS
The John/Joan case and implications for behavior Genetics
Milton Diamond
12:30 - 1:30 LUNCH
Monday July 9th
1:30 - 3:30
SYMPOSIUM I
Developmental approaches to the genetics of antisocial behaviour and adjustment problems
Organizer and Chair: Thalia Eley
Discussant: Terrie Moffitt
Longitudinal genetic analysis of aggressive and non-aggressive antisocial behavioural symptoms
Thalia C. Eley and Paul Lichtenstein
Does Parenting Really Matter? A Test of the Nurture Assumption
Jenae M. Neiderhiser and Alison Pike
Examining sex and cohort differences in the etiology of conduct disorder: A study of 6,342 adult twin pairs
Wendy S. Slutske, Andrew C. Heath, Kathleen K. Bucholz, Pamela A. F. Madden, Dixie Statham and Nicholas G. Martin
Behavioral Genetic Confirmation of a Life-Course Perspective on Antisocial Behavior: Can We Believe the Results?
Kristen C. Jacobson, Michael C. Neale, Carol A. Prescott, and Ken S. Kendler
Monday July 9th
1:30 - 3:30
SYMPOSIUM II
Laterality: Genetic and evolutionary approaches
Organizer and Chair: Pierre L. Roubertoux
Discussant: Stephen Maxson
Non-human primate patterns of manual laterality
Jacques Vauclair and Eric Damerose
ProtocadherinXY as a candidate for the Homo sapiens speciation gene
Tim Crow, Nic A Williams, Maria Giouzeli, Norman Ross, Patricia Blanco, Carole A Sargent and Nabeel A Affara
Familial study and partial genome scan for degree of laterality
Anne-Lise Doyen, Thierry Dufour, Laetitia Prut and Michele Carlier
Analysis of quantitative trait loci for behavioral laterality in mice
Pierre L. Roubertoux, Isabelle Le Roy, Danièle Migliore-Samour and Améziane Cherfouh
Genetic, neuroanatomical and behavioural approaches to studying CNS asymmetries in zebrafish
Anukampa Barth, Miguel Concha, Claire Russell and Steve Wilson
3:30 - 4:00 TEA
Monday July 9th
4:00 - 5:15
PAPER SESSION III
Methodology
Chair: Stacey Cherny
4:00 - 4:15 The analysis and statistical power of data collected from screened samples of twins
Michael C. Neale and Kenneth S. Kendler
4:15 - 4:30 The role of the Children of Twins design in highlighting genetic and environmental pathways between parental and child characteristics
Brian M. D'Onofrio, Eric Turkheimer, Linda A. Corey, Robert E. Emery, Mary Waldron and Lindon J. Eaves
4:30 - 4:45 A measurement error explanation of the biased QTL effect estimates when pi-hat is used as the IBD probability for untyped sib pairs
A. Leo Beem and Dorret I. Boomsma
4:45 - 5:00 Gene-by-environment interaction in twin and sib-pair analysis (T)
Shaun Purcell
5:00-5:15 Bayesian approaches to modeling deveopment in twins
Lindon J. Eaves and Al Erkanli
Monday July 9th
4:00 - 6:00
VISIT to SANGER CENTER
limited places only - please sign up at the registration desk
Monday July 9th
5:30 - 7:00
POSTER SESSION I
1 Genetic analysis of DSM-oriented scales in 3 year-old Dutch twins as a function of parental Socio-economic status
Tinca Polderman, Toos van Beijsterveldt, Caroline van Baal, Therese Stroet, Alexia Groot, Jolande van der Valk, Frank Verhulst, Tom Achenbach, Jim Hudziak and Dorret Boomsma
2 Genetic and environmental influences on sex-typed behavior in pre-school children: A study of 1,973 twin pairs at 3 and at 4 years of age (T)
Alessandra C. Iervolino, Melissa Hines, Susan Golombok, John Rust, Thalia Eley and Robert Plomin
3 Continuous and Discontinuous Cognitive Development (T)
Marjolein J. H. Rietveld, G. Caroline M. van Baal, Meike Bartels and Dorret I. Boomsma
4 Genetic and environmental contributions to continuity and change of behaviors at ages 3 to 7 (T)
Jolande C. van der Valk, Edwin J.C.G. Van den Oord, Frank C. Verhulst and Dorret I. Boomsma
5 Heterogeneity of childhood aggression and anti-social behavior: A twin study
Laura A. Baker, Jennifer K. Johnson, Dora I. Lozano and Adrian Raine
6 Genetic and contrast effects on temperamental difficulty and unadaptability in infancy and early childhood (T)
Kathryn S. Lemery, Nicole L. Schmidt and H. Hill Goldsmith
7 Common and unique genetic and environmental influences on EAS temperament dimensions in childhood (T)
Amber L. Gahagan and Irwin D. Waldman
8 Shared environmental transmission of culture: Methodology and findings
Juko Ando and Yutaka Ono
9 Genetic and environmental contributions of TCI subscales
Juko Ando, Naoko Onoda, Yoshimura Kimio and Yutaka Ono
10 Presence of mammary tumor virus alters the body odor of mice
Kunio Yamazaki, Gary K. Beauchamp, Judith Bard and Edward A. Boyse
11 Genetic variation for circadian activity rhythm period among eight inbred mouse strains
Bernard P. Possidente, Jennifer Wishnow, Felicia Gomez and Susan Kur
12 Quantitative Trait Loci (QTL) Analysis of Body Weight in F2 and Recombinant Inbred Mice
Holly A. Mack, Michael D. Grant, Tara K. Kerin, Jose R. Fernandez, George P. Vogler, David J. Vandenbergh and Gerald E. McClearn
13 Genetic control of skeletal maturation during growth
Martine A.I. Thomis, Hermine H.M. Maes, Maarten Peeters, Ruth Loos, Roeland Lysens, Albrecht L. Claessens, Bavo Vanden Eynde, Robert Vlietinck and Gaston Beunen
14 Evolution of genetic and environmental influences on regional fat distribution from early adolescence to young adulthood (T)
Maarten W. Peeters, Hermine H.M. Maes, Martine A. Thomis, Ruth Loos, Albrecht L. Claessens, Roeland Lysens, Bart Vanden Eynde, Robert Vlietinck and Gaston P. Beunen
15 Studies of Chromosome Sensitivities in Twin Children (T)
Kazuko Nakashima and Kanehisa Morimoto
16 Assessment of Stratification in Linkage and Association Samples
Neilson C. Martin, Goncalo R. Abecasis and Lon R. Cardon
17 An overview of regression methods of linkage analysis in selected samples
Jeffrey M. Lessem, Stacey S. Cherny, Goncalo R. Abecasis, Pak C. Sham and Shaun Purcell
18 Triton Survey Designer: A software package for the design, administration, and analysis of surveys
Ian L. Cesa, Michael King, Mo Zheng, Tina Lee, Jennifer K. Johnson and Laura A. Baker
19 Family history influences on adopted adolescents' substance experimentation
Sally-Ann Rhea and Robin P. Corley
20 Candidate Gene Studies in Substance-Dependent Adolescents, their Siblings, and Controls
Susan E. Young, Andrew Smolen, Michael C. Stallings, Robin P. Corley, Thomas J. Crowley and John K. Hewitt
21 Genetic and Environmental Transmission of Attitudes toward Alcohol Consumption
Richard J. Viken, Richard J. Rose, Jaakko Kaprio and Markku Koskenvuo
22 Genetic and environmental influences on the covariation between sensitivity and tolerance to alcohol
Jennifer K. Johnson, Richard J. Viken and Richard J. Rose
23 Common Genetic and Environmental Vulnerability for Alcohol and Tobacco Use in a Volunteer Sample of Older Female Twins
Christian J. Hopfer, Michael C. Stallings and John K. Hewitt
24 Continuity or Discontinuity between Substance Experimentation, Regular Use, and Dependence Symptoms in Adolescence: Twin and Adoption Results
Robin P. Corley, Michael C. Stallings, John K. Hewitt and Susan E. Young
25 Reading performance at 7, 12 and 16 years of age in the Colorado Adoption Project: Parent-offspring analyses
Sally J. Wadsworth, Robin Corley, John K. Hewitt, Robert Plomin and John C. DeFries
TUESDAY JULY 10
Tuesday July 10th
8:30 - 10:30
PLENARY SYMPOSIUM, PART I
New Molecular Techniques of Behavioral Genetics
Organizers and Chairs: Ian Craig and Robert Plomin
Human genome: Facts and fallacies
Ian Craig
Genetic markers: Mileposts and maps
David Bentley
Trawling the DNA bases: How to make sense of sequence
Mark Ross
The highs and lows of genome screens
Simon Fisher
10:30 - 11:00 TEA
Tuesday July 10th
11:00 - 1:00
PLENARY SYMPOSIUM, PART II
New Molecular Techniques of Behavioral Genetics
Organizers and Chairs: Ian Craig and Robert Plomin
What's new with linkage and association approaches to identifying QTLs
Pak Sham
Theory and practice of DNA pooling
Michael Owens
Looking for polymorphisms that affect gene regulation
Mick O'Donovan
Mouse models for human behavior
Lee Schalkwyk
1:00 - 2:00 LUNCH
Tuesday July 10th
2:15 - 3:30
PAPER SESSION IV
Personality
Chair: Katherine Kirk
2:15 - 2:30 Genetic simplex modeling of personality in adolescent twins
Nathan A. Gillespie and Nicholas G. Martin
2:30 - 2:45 Longitudinal analysis of measures of anxiety and depression in adult twins
Katherine M. Kirk and Nicholas G. Martin
2:45 - 3:00 Anxious genes and the EDAC design
Andrew J. Birley, Michael C. Neale, Katherine M. Kirk and Nicholas G. Martin
3:00 - 3:15 Multivariate analysis of level and lability of self-esteem
Michelle B. Neiss, Elizabeth F. Gramzow, Constantine Sedikides and Jim Stevenson
3:15 - 3:30 DRD4, psychopathology, and personality: preliminary findings from the Dunedin multidisciplinary health and development study
Jonathan S. Mill, Joseph L. McClay, Karen Sugden, Philip J. Asherson, Richie Poulton, Terrie E. Moffitt and Avshalom Caspi
Tuesday July 10th
2:15 - 3:30
PAPER SESSION V
Smoking
Chair: Pamela Madden
2:15 - 2:30 Relative risk of smoking parents and smoking siblings on smoking status (T)
Jacqueline M.Vink and Dorret I. Boomsma
2:30 - 2:45 Genetic and environmental influences on smoking initiation: An extended twin kinship analysis
Hermine H. Maes, Andrew C. Heath, Nicholas G. Martin, Michael C. Neale and Lindon J. Eaves
2:45 - 3:00 Smoking Progression Among Adolescents: A sibling study
George D. Papandonatos, Richard Rende, Ray Niaura and Elizabeth E. Lloyd
3:00 - 3:15 Toward characterization of adolescent nicotine dependence
Christina N. Lessov, Pamela A.F. Madden, Kathleen K. Bucholz, Wendy S. Slutske and Andrew C. Heath
3:15 - 3:30 The DRD4 VNTR Polymorphism Influences Reactivity to Smoking Cues
Kent E. Hutchison, Heather LaChance, Raymond Niaura, Angela D. Bryan and Andrew Smollen
3:30 - 4:00 TEA
Tuesday July 10th
4:00 - 5:15
PAPER SESSION VI
Alcohol
Chair: Andrew Heath
4:00 - 4:15 Parental Alcohol Dependence and Suicidal Behavior in Adolescent Female Twins (T)
Anne L. Glowinski and Andrew C. Heath
4:15 - 4:30 Latent Growth Curve Analyses of Drinking Trajectories Across Adolescence
Danielle M. Dick, Richard J. Viken, Jaakko Kaprio and Richard J. Rose
4:30 - 4:45 Genetics of Alcohol Dependence: Controlling for other heritable risk factors
Valerie S. Knopik, Andrew C. Heath, Pamela A. F. Madden, Kathleen K. Bucholz, Elliot C. Nelson and Nicholas G. Martin
4:45 - 5:00 Sources of covariance between alcoholism and motivations for drinking
Carol A. Prescott, Rebecca Cross, John L. Horn and Kenneth S. Kendler
5:00 - 5:15 Modeling the familial transmission of alcohol dependence symptom counts in clinical and control family pedigrees
Michael C. Stallings, John K. Hewitt, Jeff M. Lessem, Susan E. Young, Robin P. Corley, Susan K. Mikulich and Thomas J. Crowley
Tuesday July 10th
4:00 - 6:00
VISIT to SANGER CENTER
limited places only - please sign up at the registration desk
Tuesday July 10th
5:30 - 7:00
POSTER SESSION II
1 Genetic and environmental relationships between eating disorder and personality in the Japanese female twin sample
Hiroko Maekawa, Juko Ando and Yutaka Ono
2 Indirect effects of the DRD4 VNTR polymorphism on sexual desire
Angela D. Bryan, Kent E. Hutchison and Andrew Smolen
3 Is Prolonged Fatigue in Children & Adolescents Heritable? (T)
Tom A Fowler, Anita Thapar and Ann Farmer
4 Genome scan for quantitative traits involved in cardiovascular disease in three independent populations
M. Beekman, B.T. Heijmans, N. Lakenberg, E. Suchiman, G.P. Vogler, N.G. Martin, J.B. Whitfield, N.L. Pedersen, C. Kluft, G.J.B. van Ommen, R.R. Frants, P. de Knijff, E. Slagboom and D.I. Boomsma
5 Genetics of the contingent negative variation in migraine
Michael S. Siniatchkin and Wolf-Dieter Gerber
6 24-hour saliva cortisol measurements in twins and siblings selected to be at high or low genetic risk for anxious depression (T)
Mireille van den Berg, Eco de Geus, Dorret I. Boomsma, Conor V. Dolan and Clemens Kirschbaum
7 A Longitudinal Study of Japanese Adolescents' Depression and Received Parenting
Naoko Onoda, Juko Ando and Yutaka Ono
8 Extreme Depressive Symptoms in Children and Adolescents (T)
Frances J Rice, Gordon T Harold and Anita Thapar
9 A Twin Study of the Genetics of Fear Conditioning
John M. Hettema, Peter Annas, Michael C. Neale, Mats Fredrikson and Kenneth S. Kendler
10 Heritability of Depression Symptomatology in the Second Half of Life: Evidence from Danish Twins over 45 (T)
Wendy Johnson, Matt McGue, David Gaist, James W. Vaupel and Kaare Christensen
11 Reading difficulties and rapid naming: Bivariate twin and genetic linkage analyses(T)
Chayna J. Davis, Javier Gayan, Valerie S. Knopik, Shelley D. Smith, Lon R. Cardon, Bruce F. Pennington, Richard K. Olson and John C. DeFries
12 Differential genetic etiology of reading disability as a function of processing speed (T)
Rebecca J. Cross, Javier Gayan, John C. DeFries and Richard K. Olson
13 Sensory deprivation and predatory behavior in mice
Donald J. Nash, Alan Schell, Brooke Quigley, Jake Adams and Bryan Hill
14 Aggression and Mating in Sex Reversed Mice (T)
Andrew Canastar and Stephen C. Maxson
15 Factor analyses of phenotypic correlations of animal behaviors assessed in multiple test events are often not informative
Norman D. Henderson
16 A review of QTL and knock-out studies for emotionality in mice
Rens de Groot, Nico Lakenberg, Eline Slagboom, and Dorret Boomsma
17 East-West, home's best: rewarding properties of the home-cage of laboratory mice
David A Blizard, Rachel Cohen, Laura Cousino-Klein and Gerald E. McClearn
18 Investigating Age Differences in the Genetic and Environmental Structure of the TPQ in Later Adulthood (T)
Noa Heiman, Michael C. Stallings, John K. Hewitt and S.M. Hofer
19 Analysis of Twin Data of Adult Attachments
Masaki Fujimoto, Toshimitsu Kamakura, Hisako Itoi, Yuko Kobori, and Kunii Suzuki
20 Social Closeness and Familiarity in MZA and DZA Twin Pairs
Nancy L. Segal and Sara Arad
21 Genetic and environmental influences on self-esteem in a sample of middle-aged twins in Japan
Toshimitsu Kamakura, Masaki Fujimoto, Hisako Itoi, Kunitake Suzuki and Yuko Kobori
22 Genetic and environmental influences on 'theory-of-mind' in Japanese adult twins ()
Atsushi Senju, Juko Ando, Yutaka Ono, Toshikazu Hasegawa and Mariko Hiraiwa-Hasegawa
23 Is giving up smoking on the nicotine patch related to genotype?
Patricia Yudkin, Kate Hey, Sarah Roberts, Sarah Welch, Elaine Johnstone, Michael Murphy, Sian Griffiths, Lesley Jones and Robert Walton
24 Failed Smoking Cessation: Nicotine Withdrawal and Genetic Vulnerability
Hong Xian, Jeffrey Scherrer, Pamela AF Madden, Michael Lyons, Ming Tsuang, William R True and Seth A Eisen
25 The Fagerstrom Test for Nicotine Dependence in a Twin-family Study (T)
Jacqueline M.Vink and Dorret I Boomsma
26 The Genetic Basis for Tobacco Dependence: A Systematic Review
Marcus Munafo, Robert Walton, Elaine Johnstone, Patricia Yudkin, Michael Murphy, Lindsay Stead and Lon Cardon
27 A Twin and Sibling Study of Cigarette Smoking in the National Longitudinal Study of Adolescent Health
David C. Rowe and Kristen C. Jacobson
WEDNESDAY JULY 11
Wednesday July 11th
9:00 - 11:00
SYMPOSIUM III
Organizer and Chair: Stacey Cherny and Pak Sham
Discussant: Lon Cardon
The effects of genotype errors on mapping complex traits: Detection and treatment
Stacey S. Cherny, Lon R. Cardon1 and Gonzalo R. Abecasis
Optimal Selection Strategies for QTL Mapping using Pooled DNA Samples
Ansar Jawaid, Shaun Purcell, Stacey S. Cherny and Pak Sham
An index of multipoint polymorphism information content (MPIC)
Frøhling Rijsdijk and Pak Sham
Equivalence between Haseman-Elton and variance-components methods for sib-pair quantitative trait linkage analysis (T)
Shaun Purcell and Pak Sham
Wednesday July 11th
9:00 - 11:00
SYMPOSIUM IV
Tools for identifying sources of nonshared environment
Organizer and Chair: Erica L. Spotts
Discussant: Eric Turkheimer
Genetic and environmental mechanisms underlying the association between marriage and depressive symptoms (T)
Erica L. Spotts and David Reiss
The experiential context of parenting
Jody M. Ganiban
Differential Parental Negativity: Objective Reality or in the Eye of the Beholder?
Alison Pike and Jenae M. Neiderhiser
A meta-analytic review of bivariate nonshared environment (T)
Mary Waldron and Eric Turkheimer
11:00 - 11:15 BREAK
Wednesday July 11th
11:15 - 12:30
BUSINESS MEETING
12:30 - 1:30 LUNCH
Wednesday July 11th
1:30 - 3:30
SYMPOSIUM V
Molecular Genetic Studies of Dopamine Genes and ADHD
Organizer and Chair: Irwin Waldman
Discussant: Robert Plomin
Association and linkage studies of DAT1, DRD4 and other dopamine system genes in ADHD2
Philip Asherson, Sarah Curran, Jon Mill and Eric Taylor
QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms
Sarah Curran, Jon Mill, Pak Sham, Fruhling Rijsdijk, Katja Marusic, Eric Taylor and Philip Asherson
Evidence of Association between DRD4 and ADHD with conduct disturbance
Anita Thapar, Jane Holmes, Anthony Payton, Jenny Barrett, Richard Harrington, Peter McGuffin, Michael Owen, William Ollier, Michael Gill, Aiveen Kirley, Ziarih Hawi, Michael Fitzgerald, Philip Asherson, Sarah Curran, John Mill, Alison Gould, Eric Taylor, Lyndsey Kent, Nick Craddock and Jane Worthington
Association of DRD4 and measures of executive functions relevant to ADHD
Irwin D. Waldman, Yuki Hadeishi, David C. Rowe, Craig Stever, L. Nicole Giedinghagen, Jaime M. C. Gard, Jennifer H. Mohr, Stephanie Sherman and Ann Abramowitz
Wednesday July 10th
1:30 - 3:00
PAPER SESSION VII
Developmental
Chair: Richard Rose
1:30 - 1:45 A Longitudinal Study of Common Childhood Psychopathology (T)
Marjolein J. H. Rietveld, Toos van Beijsterveldt, Jolande C. van der Valk, F. C. Verhulst and Dorret I. Boomsma
1:45 - 2:00 Attention Problems and Emotionality at Ages 7 and 12
Stephanie Schmitz
2:00 - 2:15 Genetic and Environmental Influences on Pubertal Development in Males and Females
Brian S. Mustanski, Richard J. Viken, Jaakko Kaprio, Lea Pulkkinen and Richard J. Rose
2:15 - 2:30 Drosophila Kin Recognition
Yong-Kyu Kim
2:30 - 2:45 The nature of shared environmental influence on adolescent Behavioral deviance: Parent versus sibling effects
Matt McGue and William G. Iacono
2:45 - 3:00 Shared Environmental Effects on Behavior: Distinguishing Familial from Non-Familial Sources with Data from Twins and their Classmate Controls
Richard J. Rose, Richard J. Viken, Danielle M. Dick, Lea Pulkkinen and Jaakko Kaprio
3:30 - 4:00 TEA
Wednesday July 11th
4:00 - 5:00
PAPER SESSION VIII
Comorbidity
Chair: Soo Hyun Rhee
4:00 - 4:15 The etiology of comorbidity between substance dependence and conduct disorder in adolescents
Soo Hyun Rhee, John K. Hewitt, Susan E. Young, Robin P. Corley, Thomas J. Crowley and Michael C. Stallings
4:15 - 4:30 Covariation among childhood externalizing disorders: Identifying shared environmental contributions(T)
S. Alexandra Burt, Robert F. Krueger, Matthew K. McGue and William G. Iacono
4:30 - 4:45 The Relationship between Attention-Deficit/Hyperacitvity Disorder, Reading Disorder, and Communication Disorder Symptomatology (T)
Erika Hagemann, David A. Hay and Catherine L. Taylor
4:45 - 5:00 The association between depressive symptoms and common variance among metabolic risk factors for cardiovascular disease: results from the NHLBI twin study (T)
Jeanne McCaffery, Raymond Niaura, John Todaro, Dorit Carmelli and Gary Swan
Wednesday July 11th
4:00 - 6:00
VISIT to SANGER CENTER
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Wednesday July 11th
5:00 - 6:00
EXECUTIVE COMMITTEE MEETING
Wednesday July 11th
7:00
BANQUET
PRESIDENTIAL ADDRESS: Substance dependence and antisocial behavior in adolescence: the Colorado studies
John K. Hewitt
THURSDAY JULY 12
Thursday July 12th
10:00 - 12:00
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ABSTRACTS in alphabetical order by author

Maricela Alarcón1, Rita M. Cantor2, AGRE Consortium, and Daniel H. Geschwind1
Linkage Analysis of Language Traits in Autistic Families
1Department of Neurology, University of California, Los Angeles CA 2Department of Human Genetics, University of California, Los Angeles CA
Address: UCLA Department of Neurology, 710 Westwood Plaza B-105, Los Angeles, CA 90095 Phone: 310 794 4172 Fax: 310 267 2401 Email: malarcon@ucla.edu

Autism is a neuropsychiatric disorder with complex inheritance that affects about 1 in 1000 children and is characterized by deficits in language and social skills, and repetitive behaviors. Although linkage analyses of the autism diagnosis have been performed, none have focused on the behavioral traits associated with this disorder. To investigate the language component of autism, a nonparametric genome scan analysis was performed to identify quantitative trait loci (QTL) for this trait in a subset of families collected by the Autism Genetic Resource Exchange (AGRE). The AGRE families were recruited for the presence of at least two children with autism spectrum disorders using the Autism Diagnostic Interview (ADI-R; C. Lord, M. Rutter, and A. Le Couteur, 1994, J. Aut. and Dev. Dis. 24, 659-685) which was administered to the parents by pediatric neurologists to confirm the children's diagnoses and to clinically characterize them. Parents and offspring were genotyped for 335 markers and mutipoint linkage analyses were conducted using the Genehunter (L. Kruglyak, M. J. Daly, M. P. Reeve-Daly, and E. S. Lander, 1996, Am. J. Hum. Genet. 58, 1347-1363) software. The strongest evidence of linkage to a measure of language development, the ADI-R item'age at first word', was observed on chromosomal region 7q (Z = 2.98), about 25 cM away from the SPCH1 locus (S. E. Fisher, F. Vargha-Khadem, K. E. Watkins, A. P. Monaco, and M. E. Pembrey, 1998, Nat. Genet. 18, 168-170) and only 3 cM away from previously reported results for the autism diagnosis (International Molecular Genetic Study of Autism Consortium, 1998, Hum. Mol. Genet. 7,571-578). These findings suggest that the putative susceptibility region on chromosome 7 may be a QTL for language traits associated with autism.


V. Elving Anderson
Neonatal seizures, M-channels, and retigabine
Division of Epidemiology and Institute of Human Genetics, University of Minnesota, Minneapolis, MN
Address: University of Minnesota, MMC 197, 420 Delaware St SE, Minneapolis MN 55455 Phone: 612 625 3281 Fax: 612 625 8950 Email: ander087@umn.edu

The recent convergence of three independent lines of research has made it possible to trace the pathways connecting a seizure disorder, a physiological mechanism and a therapeutic agent. (1) Benign familial neonatal convulsions (BFNC) are characterized by autosomal dominant inheritance of seizures that have onset usually in the first week of life and that stop by the fourth month with some later exceptions. One gene was mapped to chromosome 20 in 1989 and a second to chromosome 8 soon thereafter. Early in 1998 two research groups reported these to be potassium ion channel genes, KCNQ2 and KCNQ3. (2) Later that year the two gene products were recognized as the major subunits of M-channels that are important in determining the excitability of neurons. When potassium leaves or chloride enters a cell, the cell interior becomes more negative, and thus less excitable. Joint expression in Xenopus oocytes of both genes yields potassium currents 11-fold higher than with either gene alone. BFNC involves mutations in either KCNQ2 or KCNQ3 that reduce the current amplitude without affecting other properties of the channels. (3) Retigabine is an anticonvulsant that recently was found to have a marked effect on KCNQ2/3 currents, causing the channels to open sooner and slowing the rate of channel closing. When mutant KCNQ2 is expressed together with normal KCNQ3, retigabine stabilizes the cells. Thus retigabine may be the first anticonvulsant to target the cause of an epilepsy syndrome by compensating the deficit of a specific channelopathy. Pharmaceutical researchers now are using KCNQ2/3 channels to identify other drugs that are selective channel openers. Conclusions: These findings show how the identification of epilepsy susceptibility genes provides new approaches to basic neurophysiological studies and to drug development. They may have implications for other disorders that affect neuronal excitability.


Juko Ando1, and Yutaka Ono2
Shared environmental transmission of culture: Methodology and findings3
1Faculty of Letters, Keio University, Mita Tokyo 2School of Medicine, Keio University, Shinanomachi Tokyo 3Supported by a Grant-in Aid for Scientific Research (C) from the Ministry of Education, Science, Sports and Culture
Address: Faculty of Letters, Keio University, 2-15-45, Mita, Minatoku, Tokyo, 108-8345, Japan Phone: 81 3 3453 4511 Fax: 81 3 5427 1578 Email: juko@msa.biglobe.ne.jp

In traditional behavioral genetics studies, it is widely recognized that shared environmental effects are negligible in general psychological traits like personality, intelligence after adolescent and psychopathology. However, it is reasonable to think that substantial shared environmental contribution would be found in cultural domains like reading, musical, athletic, artistic, and academic activities. In order to show specific shared environmental cultural transmission, the following conditions should be met: 1) one's specific cultural activity (e.g. the amount of books one reads in a week) shows shared environmental contribution, 2) a specific cultural environment related to this activity (e.g. how often one's parents recommend him/her to read books) shows shared environmental contribution, 3) this specific cultural activity (=1) is phenotypically correlated with this specific cultural environment (=2), 4) this correlation is mediated by shared environment of (1) and (2). In the present study, for example, boys' involvement of reading books (=1) and their fathers' preference of reading books (=2) showed shared environmental contributions (49% and 78%), and were significantly correlated (.17; p<.05). Multivariate analysis revealed that this correlation was mediated by shared environment (.11) more than by nonshared environment (.05).


Juko Ando1, Naoko Onoda2, Yoshimura Kimio3, and Yutaka Ono 2
Genetic and environmental contributions of TCI subscales4
1Faculty of Letters, Keio University, Mita Tokyo 2School of Medicine, Keio University, Shinanomachi Tokyo 3Cancer Information and Epidemiology Division, National Cancer Research Institute, Chiyodaku Tokyo 4Supported by a Grant-in Aid for Scientific Research (C) from the Ministry of Education, Science, Sports and Culture
Address: Faculty of Letters, Keio University, 2-15-45, Mita, Minatoku, Tokyo, 108-8345, Japan Phone: 81 3 3453 4511 Fax: 81 3 5427 1578 Email: juko@msa.biglobe.ne.jp

TCI (Temperament and Character Inventory, Cloninger et al., 1993, Archives of Genetic Psychiatry 50, 975-990) contains 25 subscales with seven higher-order dimensions (four for Temperament and three for Character). Univariate genetic analyses were conducted at subscale level with the Japanese twin sample (184 pairs of MZ and 112 pairs of DZ). CE models yielded the best fit in two subscales (NS1 and NS4)out of four in Novelty Seeking (NS), one (RD4) out of three in Reward Dependence (RD), one (SD2) out of five in Self-Directedness, and two (CO2 and CO5) out of five in Cooperativeness. For all the subscales in Harm Avoidance and Self-Transcendence, AE models were the best fit. An average contribution of additive genetic effects was .31 (range: .09-.43) whereas that of shared environment was .21 (range: .16-.34).


Philip Asherson1, Sarah Curran1, Jon Mill1, and Eric Taylor1
Association and linkage studies of DAT1, DRD4 and other dopamine system genes in ADHD2
1Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London, UK, SE5 8AF 2Research supported by UK MRC
Address: Social Genetic Developmental Psychiatry Research Centre (SGDP), Institute of Psychiatry, London, UK, SE5 8AF Phone: +44 207 848 0859/0319/0951 Fax: +44 207 848 0407 Email: p.asherson@iop.kcl.ac.uk

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focused on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs. Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein. To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the gene, five that support an association and three against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSMIV ADHD, using the transmission disequilibrium test (TDT). Results from the UK (x2=8.97, p=.0.01, OR=1.95), but not the Turkish sample (x2=0.93, p=0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (x2=3.45, p=.06, OR=1.15), however we find significant evidence of heterogeneity between the combined dataset (x2 = 22.64, df=8, p=.004). Another association of interest is between ADHD and the 7-repeat allele of a VNTR in exon 3 of DRD4. Using a case (n=132) vs. control (n=189) design we provide evidence for the putative association with 7-repeat allele (c2=6.17, 1 d.f., OR=1.73, 95% CI=1.11-2.71). A total of 85 complete trios were available for within family tests of association and linkage. TDT analysis in this subset did not confirm the association (29 transmitted versus 23 non-transmitted, c2 =0.69). We conclude that the case-control findings may be falsely positive, but can not rule out the alternative explanations of low power and gene-environment correlation. Data from other dopamine system genes (DRD5, SNAP-25, DBH) will also be presented.


Laura A. Baker1, Jennifer K. Johnson1, Dora I. Lozano1, and Adrian Raine1
Heterogeneity of childhood aggression and anti-social behavior: A twin study2
1Department of Psychology, University of Southern California, Los Angeles, CA 2Supported by MH 58354
Address: University of Southern California, Department of Psychology, 3620 S. McClintock Ave #501, Los Angeles, CA 90089-1061 Phone: 213 740 2255 Fax: 213 746 9082 Email: lbaker@usc.edu

Previous studies have found only moderate agreement between parent and child reports of children's behavior. We propose that this may be due to the global nature of the measures and inclusion of behaviors for which the parents may have little knowledge. We have begun a large scale, longitudinal twin study to address just such issues. Several measures of aggression and delinquency have been included in order to examine possible subtypes and to investigate parent-child agreement for behaviors more likely to be known to the parents. Preliminary analyses will address agreement between child self-report and parent report of children's aggressive and delinquent behavior. Constructs measured include reactive and proactive aggression, relational aggression, physical and verbal aggression, conduct and oppositional defiant disorders, and delinquency (which includes a wide range of rule-breaking behaviors). We will also examine the extent to which autonomic arousal (both cardiac and electrodermal) may show differential associations with various measures of aggression. Sex differences among different subtypes of aggressive behavior will then be explored. We will investigate the existence of mean level sex differences in physical and relational aggression. Finally, twin correlations will assess the degree to which different subtypes of aggressive and delinquent behavior are familial and will be used to estimate the relative influence of genetic and environmental factors on these behaviors.


Meike Bartels1, E.J.C. de Geus1, C. Kirschbaum2, M.J.H. Rietveld1, and D.I. Boomsma1
Daytime Basal Cortisol and Common Childhood Psychopathology3
1Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands 2Institute of Physiological Psychology II, University of Dsseldorf, Universitaetsstrasse 1, D-40225 Dsseldorf, Germany 3This work was financially supported by The Netherlands Organization for Scientific Research (575-25-012)
Address: Department of Biological Psychology, Vrije Universiteit, room 1F 57, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands Phone: +31 20 4448812 Fax: +31 20 4448832 Email: m.bartels@psy.vu.nl

Individual variation in cortisol levels plays a prominent role as a possible explanatory variable in studies on childhood psychopathology. For instance, high and low basal cortisol levels have been associated with externalizing and internalizing problem behavior, respectively, suggesting a disturbed functioning of the hypothalamic-pituitary adrenocortico (HPA)-axis in the pathogenesis of these behavioral disorders. The aim of this study is to determine whether variation in cortisol and problem behavior share the same genetic source. Toward this end, basal cortisol levels (4 samples per day on two consecutive days) and common childhood psychopathology (as assessed by the Child Behavior Checklist; CBCL) were assessed in a large sample of twelve-year-old children. The results show that heritabilities of daytime cortisol vary from weak right after awakening (h2=. 32), to moderate (h2=. 43) during the afternoon to strong (h2=. 71) during the morning peak (within an hour after awakening). Further, we observed a trend towards a negative association between cortisol and externalizing problem behavior. Whether problem behavior is a consequence of HPA-axis disregulation or a causing factor, or whether an underlying genetic defect independently gives rise to both problem behavior as well as HPA-axis disregulation, remains to be investigated. Bivariate modeling of cortisol and problem behavior could resolve this issue of the etiology causality.


Anukampa Barth1, Miguel Concha1, Claire Russell1, and Steve Wilson1
Genetic, neuroanatomical and behavioural approaches to studying CNS asymmetries in zebrafish
1Department of Anatomy and Developmental Biology, University College London
Address: Department of Anatomy and Developmental Biology, University College London, Gower St. London C1E 6BT Phone: +44 20 7679 7349 Fax: +44 20 7679 3348 Email: s.wilson@ucl.ac.uk

One of the research interests within our group is to understand the genetic pathways that lead to the establishment of differences between the left and the right sides of the brain. To achieve this, we are using a variety of neuroanatomical, genetic and behavioural approaches. In terms of neuroanatomy, we have focused upon asymmetries within the dorsal diencephalon and have shown that the photoreceptive parapineal nucleus is located on the left side of the brain and that axons from this nucleus project to the left habenular nucleus which is larger than the right nucleus. In collaboration with Becky Burdine and Alex Schier, we have shown that the Nodal pathway regulates the laterality of these asymmetries. In collaboration with Jenny Watkins, Adam Miklosi and Richard Andrew, we are now trying to determine whether the laterality of neuroanatomical asymmetries is correlated with lateralised behaviours in young zebrafish fry. To facilitate these studies, we are developing and characterising transgenic lines in collaboration with Miranda Gomperts, Enrique Amaya and Darren Gilmour. The aim of the transgenic studies is to generate fish in which GFP is used to reveal neuroanatomical asymmetries in living fish that can subsequently be used in behavioural assays. Finally, we are attempting to isolate novel mutations that disrupt CNS laterality. The best characterised of these lines is htr u28 in which affected fry show randomisation of situs. Affected fry also show reversal of some lateralised behaviours. These observations suggest that an event that determines the laterality of all embryonic tissues (endoderm, mesoderm).


M. Beekman, B.T. Heijmans3, N. Lakenberg3, E. Suchiman3, G.P. Vogler4, N.G. Martin5, J.B. Whitfield6, N.L. Pedersen7, C. Kluft1, G.J.B. van Ommen2, R.R. Frants2, P. de Knijff2, E. Slagboom3, and D.I. Boomsma8
Genome scan for quantitative traits involved in cardiovascular disease in three independent populations
1TNO Prevention and Health, Gaubius Laboratories, Dept of Vascular and Connective Tissue Research; Leiden, The Netherlands 2Dept of Human Genetics Leiden University Medical Centre; Leiden, The Netherlands 3Dept of Medical Statistics, Leiden University Medical Centre; Leiden, The Netherlands 4Center for Special Populations and Health, Pennsylvania State University; Pennsylvania, PA, USA 5Queensland Institute for Medical Research; Brisbane, Australia 6Royal Prince Alfred Hospital; Sydney, Australia 7Dept of Medical Epidemiology, Karolinska Institute; Stockholm, Sweden 8Dept of Psychology, Free University of Amsterdam; Amsterdam, The Netherlands
Address: TNO Prevention and Health, PO Box 2215 2301 CE Leiden, The Netherlands Phone: +31 71 5181403 Fax: +31 71 5181904 Email: m.beekman@pg.tno.nl

The genetic basis of cardiovascular disease (CVD) is highly complex. One strategy to dissect this is to study less complex intermediate phenotypes instead of clinical endpoints. For CVD, such intermediate phenotypes include blood pressure, plasma levels of cholesterol, apolipoproteins and triglycerides, of which more than 50% of the variation is attributable to genetic factors. The aim of our study is to map and identify genes with a major effect on these intermediate phenotypes in the general population. We are performing a genome-wide scan in population-based samples of healthy Dutch, Swedish and Australian twin pairs. We designed 80 multiplex PCR reactions randomly typing markers, with an average spacing of 18 cM, in sets of 3 to 5 chromosomes, thereby enabling statistical analyses of chromosomes during the search. Intermediate phenotypes for CVD were determined in all the twin pairs. We calculated multipoint maximum-likelihood scores using GENEHUNTER 2.0 on the data of the first scanned chromosomes. Suggestive linkage was found with total cholesterol with a maximum LOD score of 2.8 in the Dutch twin population (N=199 pairs). In the Swedish (N=53 pairs) and Australian (N=263 pairs) twin populations maximum LOD scores of respectively 1.6 and 1.0 were found in the same chromosomal region. These linkage results provide support for the presence of one locus contributing to variation of total cholesterol levels in three independent populations. It is explored how the power and QTL localisation are influenced by simultaneously analysing the populations and by genotyping parents and additional markers.


A. Leo Beem1, and Dorret I. Boomsma1
A measurement error explanation of the biased QTL effect estimates when pi-hat is used as the IBD probability for untyped sib pairs2
1Department of Biological Psychology, Free University, Amsterdam, The Netherlands 2Supported by NWO Grant 904-61-090
Address: Afdeling Biologische Psychologie, Vrije Universiteit, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands Phone: +31 20 4448811 Fax: +31 20 4448832 Email: AL.Beem@psy.vu.nl

In variance components models for QTL linkage analysis, the IBD status of sib pairs can be modeled by a mixture (or weighted likelihood) approach or by using pi-hat, the estimated expected proportion of alleles shared IBD. As QTL effects are often quite small and resources limited, marker data are mostly obtained for a selected sample of sib pairs, which are extreme concordant, discordant or both. Results from analyses that do not take the selection into account will usually be invalid. Several methods have been proposed for the analysis of such data (P.C. Sham, J.H. Zhao, S.S. Cherny and J.K. Hewitt, 2000, Genet. Epidemiol. 19, S22-S28). The analyses may include only the subjects for which marker data are available or both subjects with and without marker data. If the mixture approach is used in the full sample, the weights for the untyped subjects are the a priori probabilities for IBD zero, one and two. With the pi-hat approach, the a priori expected number of alleles shared IBD is substituted for the untyped subjects. The latter approach, which is attractive because of its simplicity, has been shown in simulations to give seriously biased estimates of the QTL effect (C.V. Dolan, D.I. Boomsma and M.C. Neale, 1999, Am. J. Hum. Genet. 64, 268-280). However, the reason for this bias remained unclear. Here the imputation of IBD probabilities will be approached as a measurement problem, in which true IBD status is estimated with various amounts of error. Obtaining consistent estimators then requires corrections for attenuation (as it is called in psychometrics). It will be demonstrated that the pi-hat approach yields the wrong correction for attenuation.


David A Blizard1, Rachel Cohen1, Laura Cousino-Klein1,2 and Gerald E. McClearn1,2
East-West, home's best: rewarding properties of the home-cage of laboratory mice
1Center for Developmental and Health Genetics 2Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, University Park, PA 16802
Address: 201, Research Building D, Pennsylvania State University, University Park, PA 16802 Phone 814 865 3429 Fax:814 863 787 Email: dab22@psu.edu

Organic deficits (e.g. food or water deprivation) or noxious stimuli (e.g. electric shock or escape from water) which are used to motivate maze learning in mice often have effects on performance which are unequally distributed across genotype and age. Thus, group differences in error scores in a maze often cannot be unambiguously attributed to variation in cognition. In the present experiment we explored the ability of a reward (return to home-cage; RHC), which does not involve manipulation of organic deficits or escape from stimuli which are clearly noxious (tissue-damaging), to motivate performance of mice in the Lashley III maze. A 2 X 2 independent groups experimental design was used to compare acquisition and retention of performance in the Lashley III maze under two reward conditions (RHC and food reward, FR) in two genetically heterogeneous groups (HS and Swiss) of male mice. The striking and unexpected finding was that RHC (N=20, Mean +/-S.E.=11.2 +/- 0.91) was as powerful a motivator of acquisition (criterion: 3 consecutive trials with one error or less per trial) as FR (N=19, 11.90 +/-0.84; RHC Vs FR, P<0.44). Furthermore, HS (9.55+/-0.57) reached criterion in fewer trials than Swiss (13.63+/-0.90;P<0.0001; no Reward X Motivational group interaction). Retention of performance after 2 weeks was excellent for most mice and did not differ significantly between reward or genetic groups. A new motivational paradigm is therefore presented which has great potential for the investigation of genetic and age-related differences in cognition. The fact that return to home-cage does not involve manipulation of organic deficits or use of noxious stimuli provides experimenters with an animal-friendly protocol that largely avoids many of the obvious confounds (e.g. differential impact of food-deprivation, differential threshold to electric shock) which are inherent in the use of the most commonly used motivators.


Dorret Boomsma1, Toos van Beijsterveldt1,2, Caroline van Baal1, Therese Stroet1, Tinca Polderman1, Alexia Groot1, Jolande van der Valk1,2, Frank Verhulst2, Tom Achenbach3, and Jim Hudziak3
Genetic analysis of DSM-oriented scales in 3 year-old Dutch twins4
1Vrije Univ, Department Biological Psychology, Amsterdam 2Erasmus Univ, Sophia Kinderziekenhuis, Rotterdam 3Univ of Vermont, College of Medicine, Burlington, Vermont 4Supported by Sophia Foundation SSWO 165, NWO-904-57-94 and NIH-R01 MH58799
Address: VU, Dept of Biological Psychology, Van der Boechorststraat 1, 1081 BT Amsterdam The Netherlands Phone: +31 20 444 8789/8786 Fax: +31 20 444 8832 Email: dorret@psy.vu.nl

We collected parental ratings of behaviOral and emotional problems with the Child Behavior Checklist (CBCL2-3) in a large sample of 3-year old Dutch twins (N = 6522 pairs). Mother's ratings of the twins' behavior was used to obtain the empirically-based CBCL syndrome scales. In addition, the recently developed scoring algorithm to obtain DSM-oriented scales was applied to the data (Achenbach & Rescorla: Manual for the ASEBA Preschool Forms & Profiles. Burlington, VT: Univ Vermont, Dept Psychiatry, 2000). The following DSM-oriented scales were constructed: affective and anxious problems, pervasive developmental problems and oppositional and overactive behavior. Results show high heritabilities for these DSM-oriented scales. For overactive behavior, genetic dominance is suggested; for the other scales there are small contributions of shared family environment.


Angela D. Bryan1, Kent E. Hutchison2, and Andrew Smolen3
Indirect effects of the DRD4 VNTR polymorphism on sexual desire4
1Department of Psychology/Institute of Behavioral Science, University of Colorado, Boulder, CO 80309 2Department of Psychology, University of Colorado, Boulder, CO 80309 3Institute for BehaviOral Genetics, University of Colorado, Boulder, CO 80309 4Supported by grants from NCI (CA81637) to the second author and from NIAAA (RO3 AA12925-01) to the first author
Address: Angela D. Bryan, Department of Psychology CB 345, University of Colorado, Boulder, CO 80309-0345 Phone: 303 735 1587 Fax: 303 492 6924 Email: angela.bryan@colorado.edu

There appears to be a reliable association between the DRD4 VNTR polymorphism and cue-elicited craving for tobacco and alcohol, and this effect seems specifically related to dopamine neurotransmission. An incentive sensitization model posits that dopamine function is a critical factor in the appetitive characteristics of drugs of abuse in general, as well as naturally appetitive stimuli including sex (Berridge & Robinson, 1998, Brain Res Brain Res Rev 28, 309-369). We conducted a pilot test assessing the generality of the effect of the DRD4 on appetitive motivation by examining its association with desire for sexual activity. We posited that the DRD4 might express its relationship to sexual desire indirectly, through personality characteristics associated with sensation/novelty-seeking. College students (N=104, 62% male) completed measures of sensation/novelty-seeking and sexual desire. Participants who were homozygous or heterozygous for the 7 repeat (or longer) allele were classified as DRD4 L and all other participants were classified as DRD4 S. A structural equation modeling analysis of the indirect effect of the DRD4 on sexual desire in EQS 5.7b indicated that the DRD4 was reliably associated with a latent sensation-seeking personality factor, and the personality factor was reliably associated with a latent measure of sexual desire. Model fit was adequate, [chi]2 (8) = 6.284, ns , CFI=1.0, RMSEA=.00 and the adaptation of the Sobel test (Sobel, 1982, in S. Leinhardt, ed., Sociological Methodology 1982, Jossey-Bass, San Francisco, CA, USA) suggested that the indirect effect of the DRD4 on sexual desire was marginally significant, p = .10. The results did not differ when gender was included in the model. These findings are suggestive of a more general association of the DRD4 with appetitive motivation not only for drugs of abuse but for naturally occurring appetitive stimuli.


S. Alexandra Burt1, Robert F. Krueger1, Matthew K. McGue1, and William G. Iacono1
Covariation among childhood externalizing disorders: Identifying shared environmental contributions 5
1Department of Psychology, University of Minnesota, Minneapolis, MN 55455 2Supported in part by NIH Grants DA05147, AA09367, AND AA00175
Address: Department of Psychology, Elliott Hall University of Minnesota, 75 East River Road, Minneapolis, MN 55455-0344 Phone: 651 645 9354 Email: burt0105@tc.umn.edu

The current study aims to expand on a previous study by Burt, Krueger, McGue, & Iacono (submitted for publication), in which we fit a biometrical model to the combined parent-child symptom counts of three common childhood disorders, specifically Attention Deficit-Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD). The results revealed that while genetic factors appeared to comprise a substantial amount of the variance within each disorder, the covariance among ADHD, ODD, and CD appeared to stem primarily from a single common environmental factor. Moreover, the shared environmental correlation was 1.0 between each pair of disorders, indicating that the same shared environmental factor influenced the presence of each of these disorders. This study hopes to directly measure this specific, shared environmental factor via measures of family functioning. Specifically, we examined the FACES-III (Olson, Portner, & Lavee, 1985, Family Adaptability and Cohesion Scale-3rd Edition (FACES-III). St. Paul: University of Minnesota), a measure of the family's perceptions of overall family functioning, and the Parental Environment Questionnaire (PEQ), a scale developed for use within the Minnesota Twin Family Study (MTFS) in which both parents and adolescents report on their parent-child relationships. The sample consists of 11 year-old male and female twins assessed as part of the ongoing MTFS (ndz=430 and nmz=844). Preliminary analyses suggest that certain aspects of the family environment, (i.e. Cohesion, as indexed by the FACES-III questionnaire, and Conflict and Regard, as indexed by the PEQ) may be contributing to the shared environmental factor that is common to ADHD, CD, and ODD.


Andrew Canastar1, and Stephen C. Maxson1
Aggression and Mating in Sex Reversed Mice2
1BioBehavioral Sciences Graduate Degree Program, The University of Connecticut, Storrs, CT 2Supported by The Inbred Mouse Fund and the Research Foundation of The University of Connecticut
Address: BioBehavioral Sciences Graduate Degree Program, U-154, The University of Connecticut, Storrs, CT 06269-4154 Phone: 860 486 2455 Fax: 860 486 3827 Email: lippachenko@hotmail.com

There are effects of the male specific part on the Y chromosome on variation in aggressive and mating behaviors of mice (S. C. Maxson, 1996, Behav. Genet 26, 471-476). There are also sex differences in these behaviors. It has been suggested that these sex differences may be in part due to the presence of this part of the Y in males and not in females (S.C. Maxson, 1997, Biomed. Rev. 7, 85-90). To test this hypothesis, these behaviors were assessed in XX females and XY females of the C57BL/6JEiYPOS strain and XY males of the C57BL/6J strain. The XY males and females are congenic. The Y of the C57BL/6JEiYPOS strain derives from Mus poschiavinus, and the Y of the XY males derives from Mus musculus. The poschiavinus Y in the C57BL/6 background results in mice with either ovaries or ovatestes. Only those with ovaries were tested. These XY females appear to be endocrinologically similar to XX females (A. J. Stavnezer, C. S. McDowell, L. A. Hyde, H. A. Bimonte, S. A. Balogh, B. J. Hoplight, V. H. Denenberg, 2000, Behav. Brain Res. 112, 135-143). Mice were tested four times for aggression against a genotype-matched opponent in an instigation paradigm (E. W. Fish. S. Faccidomo, K. A. Miczek, 1999, Psychophar. 146, 391-399). The XY males were more aggressive than the XY and XX females; there was no difference between the XX and XY females for aggression. Mice were then tested twice for mating behaviors against a C57LBL6JEi female in hormonally induced estrus. The XY males differed from both the XX and XY females in male copulatory behaviors; there was no difference between the XX and XY females for these behaviors. We suggest that although the male specific part of the Y is involved in variation among males for these behaviors, it has no effect on the sex differences in them other than in the differentiation of the primordial gonad into a testis.


Ian L. Cesa1, Michael King1, Mo Zheng2, Tina Lee2, Jennifer K. Johnson2, and Laura A. Baker2
Triton Survey Designer: A software package for the design, administration, and analysis of surveys 3
1Horizon Research Corporation, Los Angeles, CA 2Department of Psychology, University of Southern California, Los Angeles, CA 3Supported by NIMH 58354 MAIL: University of Southern California, Department of Psychology, 3620 S. McClintock Ave #501, Los Angeles, CA 90089-1061 Phone: 213 740 2255 Fax: 213 746 9082 Email: lbaker@usc.edu Internet: http://www-rcf.usc.edu/~lbaker/

This poster demonstrates the application of a powerful software package for designing and administering surveys used in the collection of data. The Triton Survey Designer is a highly flexible HTML based program that allows construction and computerized administration of surveys of varying degrees of complexity. The program interfaces with several statistical packages, including SPSS, SAS, and SPLUS, automatically providing syntax and data files for each survey. This system combines administration with data entry, therefore minimizing errors and yielding data files of improved integrity. Surveys can be easily administered by trained interviewers or respondents themselves, and can be implemented on desktops, laptops, or handheld computing devices. Thus, data collection can be done in a laboratory or in the field, or via the internet. A Triton demonstration is provided, based on interviews from the Twin Study of Social and Moral Development at USC.


Caroline Chabert1,3, Ameziane Cherfouh1, Vincent Duquenne 1, and Pierre L. Roubertoux1,2
Functional analysis of genes included in the Down syndrome chromosomal region-1 (DCR-1) with transpolygenic mice
1FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 45071 Orléans Cedex 2, France 2Universite d'Orléans, BP 6749, 45067 Orléans cedex 2 3Supported by the Fondation pour la Recherche Médicale
Address: FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 3b rue de la Ferollerie, 45071 Orléans Cedex 2, France Phone: 33 2 38 25 79 69 Fax: 33 2 38 25 79 79 Email: chabert@cnrs-orleans.fr

Down syndrome is characterized by several disorders (central nervous system, immune functions, heart). It is the main source of mental retardation (one out of 700 births). This syndrome is due to an extra copy of chromosome 21. Partial 21 trisomies have shown that patients carrying an extra chromosomal fragment of the 21q22.2-21q22.3 region was associated with most of the signs that define the syndrome (J. M. Delabar, D. Theophile, ..., and P. M. Sinet, 1993, European Journal of Human Genetics 1, 114-124). This region has been thus labeled DCR-1 (Down Chromosomal Region-1). Syntenies between chromosome 16 in mice and chromosome 21 in humans are very well documented. Ed Rubin's group has taken advantages of theses syntenies to develop transgenic mice for four chromosomal fragments covering DCR-1 (D. J. Smith, Y. Zhu, and E. M. Rubin, 1997, Nature Genetics 16, 28-36). These fragments of chromosome 21 were inserted into yeast artificial chromosomes, then incorporated into mice genome. Theses incorporations have created partial trisomy for the integrated chromosomal segment. Only the region encompassing the markers 21ES0203-21ES0291 appeared to be involved in cognitive impairments observed in these transgenic mice. Processes implicated in behavioral plasticity are particularly impaired. This region is, moreover, implicated in hind limb motor incoordinations. Neuroanatomical examinations of partial trisomic mice did not show hippocampal alterations or modifications that could be directly linked with cognitive disorders that we reported in these mice. Observations in progress could suggest that motor and cognitive disorders may have a common cerebellar origin.


Stacey S. Cherny1, Lon R. Cardon1, and Gonzalo R. Abecasis1
The effects of genotype errors on mapping complex traits: Detection and treatment2
1Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom 2Supported by NIH Grant EY-12562
Address: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom Phone: +44 1865 287590 Fax: +1 786 551 8340 Email: cherny@qtl.well.ox.ac.uk URL: http://qtl.well.ox.ac.uk/

The lack of success in mapping complex traits is a result of many factors. One potential cause is the presence of (random) errors in genotypes, which has been shown to reduce power for linkage, in some cases, quite dramatically. The robustness of a study to the effects of error depends on the sample ascertainment strategy and the method of analysis. For linkage studies, imposing random genotypes on one per cent of the assays in an unselected sample results in only a modest reduction in power, while in an affected pairs study this same error rate, which is one that would be considered low by most labs, can have the effect of transforming an otherwise adequately powered study into one which has virtually no power to detect linkage to a disease locus. Given that, it is imperative that we do our best to detect errors in our data and correct them. We discuss the effects of genotype errors on studies of linkage and association and explore the efficacy of methods for detection of errors in recovering the power lost as a result of errors, for a variety of study designs.


R. P. Corley1, M. C. Stallings1, J. K. Hewitt1, and S. E. Young1
Continuity or Discontinuity between Substance Experimentation, Regular Use, and Dependence Symptoms in Adolescence: Twin and Adoption Results2
1Institute for Behavioral Genetics, University of Colorado, Boulder CO 2Supported by grants DA-05131 and DA-11015, HD-10333, and MH-43899
Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder CO 80309-0447 Phone: 303 492 5189 Fax: 303 492 8063 Email: Robin.Corley@colorado.EDU

Heath and colleagues (A.C. Heath, J. Meyer, L. J. Eaves, and N.G. Martin, 1991, J. Stud. Alc. 52, 345-352) have suggested that abstinence from consumption is qualitatively distinct from quantity and frequency dimensions of alcohol use in adults. In adolescent substance use, it is harder to distinguish between abstinence and still-pending initiation because assessments are made during the transitional age of risk. This may result in substantial overlap between liability dimensions for experimentation, regular use, and dependence. Data on adolescent substance use has been collected from a Colorado twin sample and participants in the Colorado Adoption Project using interview and questionnaire instruments. For a measure of substance dependence that includes alcohol, tobacco, marijuana, and other drugs, adjusted for the number of substances tried, and corrected for age within gender, the correlation for 297 MZ twin pairs was 0.64, for 268 DZ twin pairs was 0.39, for 140 non-adopted sibling pairs was 0.35, and for 131 adopted sibling pairs was 0.21. We used the multiple threshold approach for ordinal data implemented in Mx to examine whether the dependence dimension could be distinguished from dimensions of use and experimentation.


Rebecca J. Cross1, Javier Gayan1, John C. DeFries1, and Richard K. Olson1
Differential genetic etiology of reading disability as a function of processing speed2
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 2This work was supported in part by program project and center grants from the National Institute of Child Health and Human Development (HD-11681 and HD-27802) to J.C. DeFries. This report was prepared while R.J. Cross was supported by NIMH training grant MH-16880.
Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309 Phone: 303 492 2817 Fax: 303 492 8063 Email: rebecca.cross@colorado.edu

There is strong evidence from Behavioral genetic studies for a significant genetic etiology in reading disability at the group level (J.C. DeFries and M. Alarcon, 1996, Mental Retardation and Developmental Disabilities Research Reviews 2, 39-47). However, genetic influence may vary in kind and amount for different individuals. In the present analyses, we show that genetic influences on reading deficits are relatively low in disabled readers who are slow in three processing speed measures: matching of target pictures to one of 5 choices (Identical Pictures), rapid naming of letters and numbers presented in rows across a page (Rapid Naming), and speed in matching strings of 4 unrelated letters and numbers to the identical string among 3 foils (Colorado Perceptual Speed). 242 MZ and 171 DZ twin pairs age 8-18 years were ascertained to have at least one member with a school history for reading disability. Probands' reading scores (a composite measure of reading recognition, reading comprehension, and spelling subtests of the Peabody Individual Achievement Test) were at least 1.5 SD below the mean of a normal-twin comparison group. The interaction between the genetic etiology of reading deficits (h2g) and probands' processing speed was tested with an extension of the DeFries and Fulker (J.C. DeFries and D.W. Fulker, 1985, Behav. Genet. 15, 467-473) basic model for assessing the group heritability of extreme scores (h2g). Interactions between speed scores and h2g for reading disability were tested with groups above and below the proband medians for speed, and with individual scores on the continuous processing-speed dimensions. The interactions were significant with the high and low speed groups for all but the Rapid Naming measure. For the composite speed measure, h2g = .31 for the slow speed group, and .86 for the high speed group (interaction p = .001). When continuous speed dimensions were employed, interactions were significant (p < .05) between h2g for reading disability and the speed dimension for all three speed measures and their composite score.


Tim Crow1, Nic A Williams1, Maria Giouzeli11, Norman Ross1, Patricia Blanco2,Carole A Sargent2, and Nabeel A Affara2.
ProtocadherinXY as a candidate for the Homo sapiens speciation gene
1University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX2University Department of Pathology, University of Cambridge
Address: University Department of Psychiatry,Warneford Hospital, Oxford OX3 7JX, United Kingdom Phone: +44 1865 226474 Fax: +44 1865 244990 Email: tim.crow@psychiatry.oxford.ac.uk

Asymmetry is the characteristic that distinguishes the brain of Homo sapiens, as a possible correlate of language, from that of the chimpanzee. Degrees of asymmetry are a determinant of cognitive ability including the acquisition of words. On the basis of observations of the deficits associated with sex chromosome aneuploidies there is a substantial case that the relevant gene is in the class that is present in homologous form on the X and Y chromosomes. Such a location is consistent with the sex differences for handedness and verbal ability that may be correlates of faster brain growth in females. The Xq21.3/Yp11.2 region of homology was generated by a translocation that occurred after the separation of the chimpanzee and hominid lineages and was subject to a subsequent paracentric inversion. Within this region a gene (protocadherinXY) has been located that belongs to a class of cell adhesion molecules that are expressed in brain and may be expected to influence axonal growth towards its target tissue. The gene sequence on the Y differs from that on the X in part as a result of chromosomal events that occurred after the translocation. Such differences could account for sex differences in cerebral asymmetry and the development of verbal ability. ProtocadherinXY is thus a candidate for the the characteristic of cerebral asymmetry that defines the species and allowed language to evolve.


Sarah Curran1 , Jon Mill1, Pak Sham1, Fruhling Rijsdijk1, Katja Marusic1, Eric Taylor1and2, Philip Asherson1
QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms
1Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London, UK 2Department of Child and Adolescent Psychiatry, GKT Medical School, London, UK
Address: Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London, UK, SE5 8AF Phone: +44 207 848 0745 Fax: +44 207 919 0407 Email: s.curran@kcl.iop.ac.uk

Current developments in molecular genetics has led to a rapid increase in research aimed at the identification of genetic variation that influences complex human phenotypes. One such phenotype that has aroused a great deal of interest is the behavioural trait hyperactivity and the related clinical disorder attention deficit hyperactivity disorder (ADHD). The driving force behind the molecular genetic research in this area is the overwhelming evidence from quantitative genetic studies, that show high heritablility (h2 = 0.7- 0.9) for the behaviours characterising the diagnosis of ADHD whether the disorder is viewed as the extreme of a normally distributed trait (i.e. categorical entity) or a continuous trait. To date, molecular studies have aimed at identifying susceptibility genes for ADHD, defined using operational diagnostic criteria, and have focused on variation within genes that regulate dopamine neurotransmission. Several studies have reported ADHD to be associated with the 7 repeat of a 48 base pair variable number tandem repeat polymorphism (VNTR) in exon 3 of the dopamine receptor 4 gene (DRD4). In this study, we take a dimensional perspective of ADHD and examine the relationship of the DRD4.7 polymorphism, in a sample of children selected from the general population on the basis of high and low scores on the 5 ADHD items of the strengths and difficulties questionnaire (SDQ) as rated by their parents. We found a significant relationship between DRD4-7 and high scoring individuals (Chi- Squares test = 8.63, p = 0.003; Odds ratio = 2.09 (95% C.I. 1.24< OR < 3.54), F statistic of 7.245, p =. 008).


Chayna J. Davis1, Javier Gayan1, Valerie S. Knopik2, Shelley D. Smith3, Lon R. Cardon4, Bruce F. Pennington5, Richard K. Olson1, and John C. DeFries1
Reading difficulties and rapid naming: Bivariate twin and genetic linkage analyses6
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 2Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 3Center for Human Molecular Genetics, Munroe Meyer Institute, University of Nebraska Medical Center, Omaha, NE 4Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK 5Department of Psychology, University of Denver, Denver, CO 6Supported by program project and center grants from the National Institute of Child Health and Human Development (HD-27802) to J. C. DeFries. This report was prepared while C. J. Davis was supported by NIMH training grant MH-16880. Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309 Phone: 303 492 7362 Fax: 303 492 8063 E-mail: davisc@colorado.edu

Children with reading deficits perform more slowly than normally-achieving readers on speed of processing measures, such as rapid automatized naming (RAN). While RAN is a well-estabilished correlate of reading performance, and the heritable nature of both reading difficulties and RAN have been supported by previous research, few studies have attempted to assess the etiology of their covariation (C. J. Davis et al., Annals of Dyslexia, submitted). Measures of RAN (numbers, colors, pictures, and letters subtests), phonological decoding, orthographic choice, and a composite variable (discrm) derived from the reading recognition, reading comprehension, and spelling subtests of the Peabody Individual Achievement Test were obtained from a total of 550 twin pairs with a positive school history of reading problems. Basic DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data (J. C. DeFries and D. W. Fulker, 1985, Behav. Genet. 15, 467-473) confirmed the heritable nature of phonological decoding (h2g = .68), orthographic choice (h2g = .67), and discrm (h2g = .57). Bivariate DF models were employed to examine the extent to which deficits in these three reading measures covary genetically with RAN. Significant bivariate heritability estimates for each of the reading measures with RAN composites (numbers and letters; colors and pictures; and total) were also obtained. Subsequently, univariate sib-pair linkage analyses confirmed the presence of a QTL on chromosome 6p21.3 for phonological decoding, orthographic choice, and discrm deficits. Bivariate linkage analyses were then conducted to test the hypothesis that this QTL for reading difficulties is also a susceptibility locus for slower performance on RAN tasks. Although the results obtained from these analyses do not provide evidence that the QTL for reading difficulties found on chromosome 6p21.3 has significant pleiotropic effects on RAN, larger samples will be necessary for adequate power to conclude that the genetic correlation between reading deficits and RAN is not due in part to the 6p QTL for reading.


Rens de Groot1, Nico Lakenberg2, Eline Slagboom2, and Dorret Boomsma1
A review of QTL and knock-out studies for emotionality in mice
1Vrije Universiteit, Department Biological Psychology, Amsterdam 2Gaubius Laboratory, TNO Prevention and Health, Leiden
Address: VU, Dept of Biological Psychology, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands Phone: +31 20 444 8789/8786 Fax: +31 20 444 8832 Email: dorret@psy.vu.nl

Anxiety-related behaviour in mice called "emotionality" has been studied extensively. We reviewed mouse QTL and knock-out studies for emotionality and combined the results with the latest knowledge of mouse and human homology (www.informatics.jax.org). Results of 24 mouse studies were ordered and used for creating maps in which the locations of QTL's and knock-out genes are shown both at mouse and human chromosomes. The combination of these two sources gives an good overview of candidate regions for emotionality in humans based on mouse studies. Mouse chromosomes 1, 10, 12, and 15 show regions with replication and are therefore candidates for further investigation. We present an overview of the literature and four mouse-human homolgy maps of the most promising regions.


Danielle M. Dick1, Richard J. Viken1, Jaakko Kaprio2, and Richard J. Rose1
Latent Growth Curve Analyses of Drinking Trajectories Across Adolescence3
1Department of Psychology, Indiana University 2Department of Public Health, University of Helsinki 3FinnTwin16 is supported by NIAAA (AA 08315 and AA 00145), and by the Academy of Finland (44069)
Address: Department of Psychology, Indiana University, 1101 E. 10th St., Bloomington, IN 47405 Phone: 812 855 4101 Fax: 812 855 4691 Email: ddick@indiana.edu

Adolescence is characterized by dramatic changes in alcohol use. At age 16, the average adolescent reports drinking about once every two months; by age 18, drinking frequency has increased to a couple of times per month. We employed latent growth curve analyses to study drinking trajectories across this age range in a population-based sample of Finnish twins, Finntwin16. With genetically informative data, latent growth curve analyses permit one to investigate the extent to which variations in (1) the intercept, or mean level of drinking, and (2) the slope, representing change in the trait over time, are due to genetic and environmental influences. We applied these models to data from >1200 same-sex twin pairs from Finntwin16who were concordantly drinking at age 16. The slope for both males and females was positive, indicating that individuals with higher levels of drinking at 16 also had a steeper increase in drinking across time. In both males and females, genetic factors largely accounted for variation in mean levels of drinking, with no evidence of common environmental effects. However, in females, environmental factors were primarily responsible for changes in drinking trajectories, while genetic factors were more influential in males' changes across time. These findings support developmental theories proposing that girls are more sensitive to environmental pressures than are boys. Extensions of these analyses, such as the inclusion of other traits and environmental factors, will be discussed.


Brian M. D'Onofrio1, Eric Turkheimer1, Linda A. Corey2, Robert E. Emery1, Mary Waldron1, and Lindon J. Eaves2
The role of the Children of Twins design in highlighting genetic and environmental pathways between parental and child characteristics
1Psychology Department, University of Virginia,, Charlottesville, VA 22904-4400 2Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA 23298-0003
Address: Psychology Department, University of Virginia, 102 Gilmer Hall, PO Box 400400, Charlottesville, VA 22904-4400 Phone: 804 982 4750 Email: briand@virginia.edu

Most studies examining the relationship between parents and children rely only on correlational data, but simple epidemiological correlations may represent a multitude of different underlying pathways. The Children of Twins (COT) design helps distinguish between the possible intergenerational pathways by delineating the associations into those due to common genetic factors, common shared environmental factors, and common nonshared environmental factors. Common intergenerational genetic factors, an example of passive gene-environment correlation, and common shared environmental factors are non-causal pathways. Only the common nonshared environmental pathway, which includes the measured parental variable, suggests a causal relationship between the two variables. Therefore, the COT design provides a powerful study of parental influences on children by controlling for genetic and shared environmental effects which hinder correlational studies of parents and children. The current study utilizes the COT design to investigate the relationship between parental smoking and child birth weight in samples of same-sex twins from Norway and the United States. Multiple children from each family are included in order to increase the power of estimating the intergeneration coefficients and to test for familial influences that effect birth weight but not parental smoking. Limitations of the COT design and future directions will also be discussed.


Anne-Lise Doyen1, Thierry Dufour2, Laetitia Prut1, and Michele Carlier1
Familial study and partial genome scan for degree of laterality
1FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 45071 Orléans cedex 2, France 2Service de Neurochirurgie, Centre Hospitalier Regional d'Orléans, 45067 Orléans cedex 2, France
Address: FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 3B rue de la Ferollerie, 45071 Orléans cedex 2, France Phone: +33 238 257972 Fax: +33 238 257979 Email: al-doyen@cnrs-orleans.fr

We undertook a study to determine chromosomal regions involved in degree of laterality in Human. We recruited 94 informative families on the following criteria: they included at least two self-professed left-handers or ambidextrous either in two generations or in the same generation (having a genetic proximity of 50 %). Laterality was assessed with four tools: a reaching card task, a pegmoving task, the Purdue Pegboard and a manual preference questionnaire (for metric qualities see A.-L. Doyen and M. Carlier, In press in Laterality). Families were then proposed to participate to the genetic study, giving blood samples or buccal cells: 52 among 94 agreed to follow the molecular study. Familial resemblance was estimated in the whole sample by intraclass correlation coefficients and regression analyses: quantitative genetics showed a large father/child resemblance for the degree of laterality. This may indicate an implication of the homologous region of X and Y chromosomes in laterality (S. H. Laval, J. C. Dann, ..., and T. J. Crow, 1998, Am. J. Med. Genet. 81, 420-427). Four STSs (DXS8030, DXS1217, DXS1203 and DXS8034) were used to mark out this region. A link between the degree of laterality and DXS1203 marker was found (p< .05) and will be confirmed with a larger sample. In the same time we focused on another chromosomal region, synthenic between murine and human genomes, following previous results obtained in mice in the lab.


Thalia, C. Eley1, and Paul Lichtenstein2
Longitudinal genetic analysis of aggressive and non-aggressive antisocial behavioural symptoms
1Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London UK 2Department of Medical Epidemiology, Karolinska Institute, Sweden 3This study was funded by the Swedish Council for Social Research (project F0129/1999). Thalia Eley is supported by a UK Medical Research Council Fellowship.
Address: Social, Genetic and Developmental Psychiatry Research Centre, 111 Denmark Hill, Institute of Psychiatry, De Crespigny Park, London SE5 8AF Phone: +44 20 7848 0863 Fax: +44 20 7848 0866 E-mail: t.eley@iop.kcl.ac.uk

Recent theories on the development of antisocial behaviour (ASB) in children and adolescents suggest greater genetic influence on aggressive ("life-course persistent") as compared to non-aggressive ("adolescent limited") ASB (e.g. T. E. Moffitt, 1993, Psych. Rev. 100, 674-701). Recent twin studies including previous analyses from this study confirmed higher heritability for aggressive as compared to non-aggressive ASB symptoms, especially in girls (T. C. Eley, P. Lichtenstein, and, J. Stevenson, 1999, Child Dev. 70, 155-681). Data are now available from a second time point which replicate and extend these results. The Child Behavior Checklist was completed by the parents of over 1000 Swedish twin pairs aged 7-9 years and again at age 13-14 years. Aggressive ASB showed greater continuity from time 1 to time 2 as compared to non-aggressive ASB. Genetic factors had a greater influence on aggressive ASB than non-aggressive ASB at both time points. Shared environment influences were significant for non-aggressive ASB. There were also significant sex differences in the etiology of non-aggressive antisocial behavior at both time points. Continuity in aggressive antisocial behavior symptoms from time 1 to time 2 was largely mediated by genetic influences at both time points, whereas continuity in non-aggressive antisocial behavior was mediated by the shared environment for boys, and largely by genetic influences in girls. These data provide further support for the hypothesis that aggressive ASB is a stable heritable trait as compared to non-aggressive behavior which is more strongly influenced by the environment and shows less stability over time.


Tom A Fowler1, Anita Thapar1, and Ann Farmer2
Is Prolonged Fatigue in Children & Adolescents Heritable?
1Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, Wales 2Social, Genetic & Developmental Research Centre, Institute of Psychiatry, London, England 3Supported by PPP Healthcare Medical Trust Grant 1206/192
Address: Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, Wales, CF14 4XN Phone: +44 29 20742201 Fax: +44 29 20747839 Email: fowlerta@cf.ac.uk

Disabling Fatigue in children is a cause of serious concern, with epidemiological research showing that up to 15% of referrals to paediatric infectious disease centres (B.D. Carter & G.S. Marshall, 1995, Current Problems in Pediatrics 25, 281-93) and 42% of all medically certified long-term sickness absence from school (E.G. Dowsett & J. Colby, 1997, Journal of Chronic Fatigue Syndrome 3, 29-41) is due to fatigue. Previous work (A. Farmer, J Scourfield, N. Martin, A. Cardno & P. McGuffin, 1999, Psychol. Med. 29, 279-282) provides evidence that disabling fatigue is familial, but could not significantly differentiate between an AE model a CE model. A questionnaire on fatigue was sent to the main carer's of twins, aged 8-17 years, in 2 population based twin registries. Data were collected for 557 monozygotic (MZ) and 789 dizygotic (DZ) pairs. The results concurred with previous research in that disabling fatigue in childhood of more than a few days is highly familial. Using model fitting an AE model provided the most acceptable explanation of the variation in the twin population. For fatigue lasting over a month, a CE model was the most acceptable model, however the role of additive genetics could not be conclusively rejected. Member


Masaki Fujimoto, Toshimitsu Kamakura, Hisako ItoiYuko Kobori, and Kunii Suzuki
Analysis of Twin data of Adult Attachments
1Faculty of Humanity, Tokyo Seitoku University 2Faculty of letters, University of Chiba 3Department of Psychology, Tokyo Gakugei University 4Department of Psychology, Tokyo Gakugei University 5Graduate Course, Tokyo Metropolitan University
Address: Hisako Itoi Department of Psychology, Tokyo Gakugei University Phone: +81 422 51 4458 Fax: +81 422 51 4458 Email: itoi@u-gakugei.ac.jp

The purpose of the present study is to examine the mechanism of Attachment in genetic and environmental influences using Japanese twin sample. We apply Behavioral genetic analyses to the corresponding covariance data examining genetic and environmental influences on Adult Attachment in Japanese twin. The development of Attachment, as the relationship between self and others, influences on shaping personality. Bartholomew and Holowitz (1991) have generated a four-group taxonomy based on a 2 classification of self positive or negative) and others ( positive or negative). Many Behavioral genetic studies have done to examine the genetic and environmental influences on self and other cognition. We elucidate the mechanism of Adult Attachment in genetic and environmental influences using Japanese twin sample.


Amber L. Gahagan1, and Irwin D. Waldman1
Common and unique genetic and environmental influences on EAS temperament dimensions in childhood
1Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA 30322
Address: mailing address - Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA 30322 Phone: 770 986 7715 Fax: 404 727 0372 Email: agahaga@emory.edu

Behavior genetic studies have consistently revealed genetic influences on childhood temperament. Because of difficulties in obtaining self-reports from young children, these studies have relied primarily on parental reports. Parental reports may lead to biases in the results of these studies, however. For example, contrast effects have been implicated in parent ratings of temperament. Using the most widely used measure of childhood temperament, Buss and Plomin's Emotionality, Activity, and Sociability (EAS) scale, we collected data on 844 twin pairs (54% DZ, 46% MZ) born in Georgia. Our sample is 49% male and 51% female, and 82% of the twin pairs are Caucasian, 11% African American, 1% Hispanic and 6% of mixed ethnicity. The twins were on average 10.6 (range 4.5-17.85) years old when twins were rated by their parents on the 20-item EAS questionnaire. We first performed univariate behavior genetic analyses of the four temperament dimensions (Emotionality, Activity, Sociability, and Shyness) to examine the pattern and magnitude of genetic and environmental influences, taking into account potential contrast effects. We then conducted multivariate behavior genetic analyses of the temperament dimensions to examine whether the EAS scales share common genetic and environmental underpinnings. Significant positive phenotypic correlations between the Emotionality and Shyness scales and the Activity and Sociability scales suggest common genetic or environmental influences may account for these relations. It has been suggested that temperament dimensions may be differentially predictive of later outcomes, thus understanding more explicitly the influences on each dimension and the relations among the dimensions may have implications for understanding the specific relations between temperament dimensions and later outcomes.


Michael J. Galsworthy1, Jose L. Paya-Cano1, Lin Liu1, Santiago Monleon2 and Robert Plomin1
General Cognitive Ability (g) in Mice as the basis of a Functional Genomics Model of Cognitive Abilities and Disabilities
1SGDP, Institute of Psychiatry, King's College London, UK 2Facultad de Psicolog¡a, Avda. Blasco Ib ¤ez, Valencia, Spain
Address: SGDP, 111 Denmark Hill, London, UK, SE5 8AF Phone +44 20 7848 0407 Fax: +44 20 7848 0866 Email: m.galsworthy@iop.kcl.ac.uk

One of the best-documented facts about human cognitive abilities is that diverse abilities intercorrelate, indicating that many learning and memory processes are general (molar) rather than specific (modular). What such diverse tests have in common is termed general cognitive ability (g). In the human species g accounts for about 40% of the variance across diverse cognitive processes from IQ tests to working memory tasks and cognitive reaction time measures. Quantitative genetic research has shown that g is substantially heritable, and QTLs associated with general and specific cognitive function are already being nominated. Recent work by ourselves and collaborators indicates the presence of a general cognitive ability in mouse as well as man, which opens the opportunity for a functional genomics model of g. We have developed an efficient battery of measures that will make it possible to assess g in large samples of mice needed for genetic analysis while controlling for variables such as motor activity and emotionality. We are using heterogeneous stock (HS) mice, outbred for over 60 generations from eight inbred strains, in order to capture greater genetic variability and to provide finer resolution for QTL mapping than possible with the use of inbred strains. In our first studies of 40 HS mice, we found our cognitive tasks intercorrelated on average 0.2 and all loaded positively on a first factor that accounted for over 30% of the variance, indicating the presence of g. Our ongoing work aims to greatly increase the sample size in order to confirm these preliminary results and to begin QTL analyses of 'g' in mice. Our QTL analyses will focus on polymorphisms in candidate genes nominated by human QTL and mouse knockout literature.


Jody M. Ganiban 1
The experiential context of parenting2
1Department of Psychology, George Washington University,Washington DC,20052 2 Twin Mom Study NIMH RO1MH54610
Address: 2125 G St NW, Washington, DC 20052 Phone 202 994 7571 Fax: 202 994 1602 Email: ganiban@gwu.edu

This study explored the experiential determinants of parenting. We hypothesized that non-shared environmental contributions to mothers' warmth and negativity towards their adolescent children are explained by the women's marital relationships, and by their children's characteristics. Participants included 326 pairs of adult female Swedish twins (MZ=150; DZ=176), their partners and one adolescent child. Questionnaires were mailed to female participants prior to a home visit. During the home visit, mothers were observed during separate 10-minute interactions with their children, and with their husbands. Trained observers rated marital warmth, marital conflict, maternal warmth, and maternal negativity during the problem solving interactions. Children's characteristics were rated by their mothers and fathers. Preliminary analyses suggest that the emotional quality of the women's marital relationships and their children's characteristics partially explain non-shared environmental contributions to maternal warmth and negativity.


Nathan A. Gillespie1, and Nicholas G. Martin1
Genetic simplex modeling of personality in adolescent twins
1Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia
Address: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Brisbane QLD 4029, Australia Phone: +61 7 3362 0226 Fax: +61 7 3362 0101 Email: nathanG@qimr.edu.au

We investigated the relative stability and magnitude of genetic and environmental effects underlying major dimensions of personality across time. As part of an ongoing study of nevus risk factors and cognitive development, the Junior Eysenck Personality Questionnaire was administered to around 600 twin pairs at ages 12, 14 and 16. Data was analyzed using genetic simplex modeling which explicitly takes into account the nature of longitudinal data. Results and limitations of the methodology are discussed.


Anne L. Glowinski1, and Andrew C. Heath1
Parental Alcohol Dependence and Suicidal Behavior in Adolescent Female Twins2
1Department of Psychiatry, Washington University, St. Louis, Missouri, 63108 2Supported in part by NIH grants AA-11998, AA-09022, AA-07728, AA-07580 and the Klingenstein Third Generation Foundation Fellowship Award in Depression
Address: Dr. Anne L. Glowinski, Washington University School of Medicine Campus Box 8134 Department of Psychiatry, 40 N. Kingshighway, Suite 1,Saint Louis, MO 63108 Phone: 314 286 2217 Fax: 314 286 2213 Email: glowinsa@matlock.wustl.edu

As noted in a comprehensive review of research findings by J. Johnson and M. Leff (1999, Am. Acad. Pediat. 103, 1085-1099. Supplement to Pediatrics, Part 2 of 2, May 1999) the documentation of poor outcomes and increased risk for psychopathology in Children of alcoholics (COAs) has been done by many, yet studies allowing the examination of both genetic and environmental effects on these outcomes were scant till recently. Data from 3418 Missouri female adolescent twins with a mean age of 15.5 at assessment (947 MZ and 692 DZ pairs) and at least one of their parents were analyzed to examine the relationship between parental alcoholism (alcohol dependence or AD) and offspring suicidal behavior (defined as persistent suicidal ideation or a suicide attempt). These subjects were interviewed with a telephone version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) (which includes a separate section for the assessment of lifetime suicidal behavior) for the Missouri Female Adolescent Twin Study (MOAFTS), a population-based prospective twin-family study of alcohol use and problems and psychiatric comorbidity in young females. With logistic regression analyses, major predictors of suicidal behavior included Major Depressive Disorder (MDD), a history of childhood abuse, AD and parental AD ( with 46.1% of the subjects reporting a suicide attempt having at least one alcohol dependent parent). When twin pairs were stratified by parental history of alcoholism, we found significantly elevated heritability of suicidal behavior: 54% (95%CI: 42.6-62.9) compared to families with no parental alcoholism: 27.1% heritability (95%CI: 15.6-36.2). These results imply important genotype x environment interaction effects with the underlying genetic vulnerability particularly likely to lead to suicidal behavior, in the adverse environments (which include an increased risk of childhood abuse and other traumatic events) more commonly found in association with parental alcoholism.


Erika Hagemann1, David A. Hay1, and Catherine L. Taylor1
The Relationship between Attention-Deficit/Hyperacitvity Disorder, Reading Disorder, and Communication Disorder Symptomatology
1School of Psychology, Curtin University of Technology, Perth Western Australia
Address: School of Psychology, Curtin University of Technology, GPO Box U1987, Perth Western Australia, Australia 6845 Phone: +61 8 9266 2944 Fax: +61 8 9266 2464 Email: e.hagemann@curtin.edu.au

Although Attention-Deficit/Hyperactivity Disorder (AD/HD) is recognised as the most common childhood onset behavioural disorder affecting up to 10% of children and adolescents (M.L. Wolraich, J.N. Hannah, T.Y. Pinnock, A. Baumgaertel, and J. Brown, 1996, J. Am. Acad. Child Adolesc. Psychiatry 35, 319-324), many issues are yet to be clarified in regards to symptomatology, gender, age and co-development with other disorders. This twin study explored the relationship of Reading Disorder and Communication Disorder symptomatology to the DSM-IV subtypes of AD/HD. Participants for this study were recruited from the Western Australian (WA) Twin Register, a population-based register of families with multiple birth children born in WA between 1980 and 1992. Following exclusion of known significant physical, sensory, or intellectual handicap, or birth defects in one or more of the twins, a sample of 449 families with twins born between 1981 and 1984, and 1988 and 1989, were approached for this study. At least one full sibling, closest in age to the twin pair, and one of the twin pairs' biological parents were also ascertained and included in the study. Self report and parent report questionnaire data of symptomatology of AD/HD, Reading Disorder, and Communication Disorder were obtained. For validation, a sub-sample of families who participated in this questionnaire survey received individual follow-up assessment. Taking both twin-singleton and age effects into account, a series of bivariate and multivariate genetic and environmental structural equation models investigated underlying mechanisms for the co-occurrence and co-development of AD/HD, Reading, and Communication Disorder symptomatology. Of particular interest in the models was whether the dimensions or subtypes of DSM-IV AD/HD actually represented discrete subtypes with specific causes and comorbidity patterns. As the symptomatology of the disorders investigated are more frequent in twins than singletons and differ between genders, significant issues arise in determining models most appropriate for the general population.


Noa Heiman1, Michael C. Stallings1, John K. Hewitt1, and S.M. Hofer2
Investigating Age Differences in the Genetic and Environmental Structure of the TPQ in Later Adulthood3
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 2Center for Dev. & Health Genetics, Pennsylvania State University, University Park, PA 16802 3Supported by NIH Grant AG-17949
Address: Institute for Behavioral Genetics Campus Box 447 University of Colorado, Boulder CO 80309-0447 Phone: 303 735 2428 Fax: 303 492 8063 Email: noa.heiman@colorado.edu

Although there is considerable literature examining the development of personality constructs from childhood to adulthood, there is a paucity of research investigating age-related personality changes in later adulthood. In this study we examined cross-sectional age differences in means, phenotypic covariance structure, and the underlying genetic and environmental structure of four personality constructs from Cloninger's personality system (C.R. Cloninger, 1986, Psych. Dev. 3, 167-226): Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS). Study participants were 2770 same-sex female twins between the ages of 50 and 96 (626 MZ twin pairs plus 480 singletons; 307 DZ twin pairs plus 424 singletons), drawn from the American Association of Retired Persons (AARP) twin sample. Personality assessments were obtained through mail-out questionnaire surveys. Age differences were examined by comparing younger (age 50-66) and older (age 67+) cohorts (based on a median split of the sample), as well as estimating model parameters as linear and quadratic functions of continuous age. Results of cohort comparisons indicated modest, but significant (approximately 15-20% of a SD), declines in mean levels for NS, RD and PS. No significant mean difference was found for HA. Phenotypic variances were equivalent across age cohorts for all of the personality dimensions except NS, which showed a 15% decline in the older cohort. The relative proportions of phenotypic variance accounted for by genetic and environmental influences were also equivalent across the two age cohorts for HA, RD and PS. Only NS showed significantly higher heritability in the older cohort, while shared environment made a greater contribution in the younger cohort. Analyses using age as a continuous moderator variable confirmed the cohort comparison findings. In sum, with the exception of NS, the genetic and environmental architecture of Cloninger's personality dimensions showed minimal age differences across this age range.


Norman D. Henderson1
Factor analyses of phenotypic correlations of animal behaviors assessed in multiple test events are often not informative2
1Department of Psychology, Oberlin College, Oberlin, OH 44074 2Supported by NIMH Grant MH-53480
Address: Department of Psychology, Severance Laboratory, Oberlin College, Oberlin, OH 44074 Phone: 440 775 7695 Fax: 440 775 8356 Email: fhenders@oberlin.edu

Since the 1930's, animal researchers have been factor analyzing phenotypic correlation matrices of Behavioral measures assessed in multiple test events either test batteries or repeated tests in the same apparatus. It has been a steady but only marginally successful enterprise. Results using multiple measures from each of two or more test situations frequently produce "instrument factors" that account for most of the factor variance. Similarly, factor analyses of multiple measures obtained repeatedly from the same apparatus often suggest that the test apparatus is measuring different constructs in the repeated sessions. Covariance among Behavioral measures taken during a test event can be ascribed to genetic influences, pre-test environmental (i.e., rearing and treatment) history and unique test environment factors. Covariance created by genetic and pre-test environment can exist across different test events, whereas unique test environment covariance cannot. Using environmental correlations among 90 measures obtained within genetically homogenous mouse strains, we found that unique test environment covariance can often be the dominant contributor to phenotypic covariance among measures taken simultaneously, whereas this contribution is necessarily zero across different test events. As a result, factor analyses of phenotypic correlation matrices can be highly misleading in situations where genetic variation and/or the effects of pre-test environmental treatments are not substantial on the behaviors examined.


John M. Hettema1, Peter Annas2, Michael C. Neale1, Mats Fredrikson3, and Kenneth S. Kendler1
A Twin Study of the Genetics of Fear Conditioning
1Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 2Roche AB, Stockholm, Sweden 3Department of Psychology, Uppsala University, Uppsala, Sweden
Address: Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298-0126 Phone: 804 828 8592 Fax: 804 828 1471 Email: jhettema@hsc.vcu.edu

Phobias represent one of the most common psychiatric disorders, and the relationship between fears and phobias has long been a subject of psychiatric study. Fear conditioning via aversive learning is one well-established model for the acquisition of fears and phobias. Also, Behavioral treatment paradigms are based on the related processes of habituation and extinction, yet little is known regarding their underlying genetic structure. A unique sample of classical fear conditioning data has been obtained from 90 monozygotic and 83 dizygotic same-sex twin pairs. Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure is the electrodermal skin conductance response. We used univariate and multivariate structural equation modeling of the three conditioned phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors are responsible for and shared between these three processes.


Christian J. Hopfer1, Michael C. Stallings2, and John K. Hewitt2
Common Genetic and Environmental Vulnerability for Alcohol and Tobacco Use in a Volunteer Sample of Older Female Twins3
1University of Colorado Health Sciences Center, Denver, CO 80262 2Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 3Supported by NIDA grants DA 09842, DA 11015, DA 12845, DA 00357
Address: Box C-268-35. Dept. of Psychiatry. University of Colorado Health Sciences Center, Denver, CO 80262 Phone: 303 315 0798 Fax: 303 315 0394 Email: Christian.Hopfer@uchsc.edu

Objective: We report patterns of genetic and environmental correlations for alcohol and tobacco use in a volunteer sample of older, Caucasian, female twins using three different levels of severity for alcohol use and smoking. The levels of severity for alcohol use and smoking were: ever drank, weekly drinking, problematic drinking; ever smoked, daily smoking of a half-pack or more, and daily smoking of at least 1 pack or more. Procedures: A community-based sample of 1,926 female twins aged 50 to 96 were recruited through advertisements in the journal of the American Association of Retired Persons. Subjects were asked to rate alcohol and tobacco use over their lifetime. Analyses: Twin correlations for alcohol and tobacco use measures were fit using Mx. Results: There were significant genetic correlations between problem drinking and ever smoking and using at least one half pack per day. Rg = 1.0 (95% CI .32 ?1.0) for Problem Drinking/ Ever Smoking; and Rg = 1.0 (95% CI .43 ?1.0) for Problem Drinking/ Smoking at least .5 packs/ day. Importance of Findings: The shared genetic influence on alcohol use and smoking in women, is clearest for those subjects with the highest severity of alcohol use, problem drinking.


Kent E. Hutchison1, Heather LaChance1, Raymond Niaura2, Angela D. Bryan1, and Andrew Smollen3
The DRD4 VNTR Polymorphism Influences Reactivity to Smoking Cues4
1Department of Psychology, University of Colorado, Boulder, CO 80309 2Center for Preventive and Behavioral Medicine, Miriam Hospital and Brown University, Providence, RI, 02912 3Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 4Supported by a grant from NCI (CA81637) to the first author
Address: Department of Psychology CB 345, University of Colorado, Boulder, CO 80309-0345 Phone: 303 492 3298 Email: kenth@psych.colorado.edu

Recent research has indicated that craving for tobacco can be reliably elicited by exposure to cues associated with smoking, suggesting that cue-elicited craving for tobacco is a potentially powerful phenotype for research on genetic factors related to nicotine dependence. Given the potential role of dopamine in cue-elicited craving, the present study examined whether the DRD4 VNTR polymorphism, which putatively expresses functional differences in dopamine (D4) receptors, is associated with cue-elicited craving for tobacco. Participants who were homozygous or heterozygous for the 7 repeat (or longer) allele were classified as DRD4 L and all other participants were classified as DRD4 S (short allele). Participants were exposed to smoking cues before smoking either high nicotine cigarettes or control cigarettes. Analyses suggested that participants in the L group demonstrated significantly greater craving, more arousal, less positive affect, and more attention to the smoking cues than did the participants in the S group. DRD4 classification did not influence subjective aversive effects or positive affect after smoking, although there was some evidence that the polymorphism moderated the effects of smoking on arousal. These findings suggest that individuals with the 7 repeat allele experience greater reactivity to smoking cues and may benefit more from interventions that target dopamine receptors. (pending)


Alessandra C. Iervolino1, Melissa Hines2, Susan Golombok2, John Rust2, Thalia Eley1, and Robert Plomin1
Genetic and environmental influences on sex-typed behavior in pre-school children: A study of 1,973 twin pairs at 3 and at 4 years of age
1Social, Genetic & Developmental Psychiatry Research Centre, Institute of Psychiatry, DeCrespigny Park, London SE5 8AF, U.K., 2City University, School of Social Sciences, Northampton Square, London, EC1V 0HB, U.K
Address: Institute of Psychiatry, SGDP Research Centre, 111 Denmark Hill, London SE5 8AF, United Kingdom Phone: +44 207 848 0629 Fax: +44 207 848 0866 Email: A.Iervolino@iop.kcl.ac.uk

Research on the development of sex-typed behavior has focused on average differences between boys and girls rather than individual differences within the sexes. We report the first prospective twin study of individual differences in sex-typed behavior in childhood. Genetic and environmental sources of individual variation were assessed for masculine and feminine sex-typed behavior at 3 and again at 4 years of age as measured by parent reports on the Pre-school Activities Inventory (Golombok, S. & Rust, J. (1993). The pre-school activities inventory: A standardized assessment of gender role in children. Psychological Assessment 5, 131-6) in a sample of 1,973 twin pairs. Model-fitting genetic analyses revealed significant genetic influence for both masculinity and femininity in boys and girls at 3 and 4 years accounting for 11-44% of the variance. Shared environmental influences accounted for 35-76% of the variance. Sex-limitation models were also fit to the data and indicated sex-specific shared environmental effects in the etiology of both masculinity and femininity. These findings suggest that although genetic factors influence the development of sex-typed behavior, shared environmental influences are more important in shaping sex-typed behavior.


Kristen C. Jacobson1, Michael C. Neale1, Carol A. Prescott1, and Ken S. Kendler1
Behavioral Genetic Confirmation of a Life-Course Perspective on Antisocial Behavior: Can We Believe the Results?
1Department of Psychiatry, MCV/VCU, Richmond VA
Address: Virginia Institute for Psychiatric and Behavioral Genetics MCV/VCU 800 E Leigh Street PO Box 980126-0126, Richmond VA 23298-0126 Phone: 804 828 8126 Fax: 804 828 1471 Email: jacobson@physio.vipbg.vcu.edu

This study examined whether the genetic and environmental architecture of adolescent antisocial behavior (AB) varied depending upon later incidence of adult AB. Data were from 1070 adult male-male twin pairs from the Virginia Stress and Coping Project. Adolescent AB was measured as self-report of number of conduct disorder symptoms prior to age 18. Individual twins were divided into two groups on the basis of their adult AB (age 18 and older): adult antisocials (AA), characterized by self-report of 2 or more symptoms of adult AB, versus adult non-antisocials (NA), characterized by self-report of 0 or 1 symptoms ofadult AB. Correlations for adolescent AB among DZ twins ranged from .25 to .29, regardless of subsequent adult AB. In contrast, correlations for adolescent AB were higher among AA-concordant MZ twins (.49) than for NA-concordant MZ twins (.39), suggesting that genetic influence on adolescent AB varies as a function of later adult AB. The MZ correlation among twins discordant for adult AB was .16. Multiple group analysis using Mx confirmed that genetic and environmental influences on adolescent AB significantly differed across the two groups (LRC=8.57, df=2, p<.05). Among the AA twins, heritability of adolescent AB was .38, and shared environmental influences = .10. In contrast, among NA twins, heritability =.00 and shared environmental influences =.35. These results indicate that genetic influences on adolescent AB are significant only for those individuals who engage in adult AB, consistent with a life-course perspective on AB. Subsequent explorations of the data revealed that the higher MZ correlation among twins concordant for the presence of adult AB could not be explained by differences in variance across the two groups, by the number of adult AB symptoms used to discriminate between groups, or by the correlation between adolescent AB and adult AB.


Ansar Jawaid12, Shaun Purcell1, Stacey S. Cherny2, and Pak Sham1
Optimal Selection Strategies for QTL Mapping using Pooled DNA Samples
1Institute of Psychiatry, King`s College London, London, SE5 8AF 2The Welcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN
Address: Psychological Medicine, Institute of Psychiatry, Decrespigny Park, Denmark Hill, London, SE5 8AF Phone: +44 20 7848 0331 Fax: +44 20 7701 9044 Email: a.jawaid@iop.kcl.ac.uk

Disequilibrium mapping is an essential tool in the identification of genes underlying complex traits. DNA pooling is a technique that allows one to perform a case-control association study without genotyping the individual DNA samples, but rather a single pool of cases and a single pool of controls. Selecting from the extremes of the trait distribution for analysis greatly enhances power in a sample. However, from where in the trait distribution should the "cases" and "controls" be selected from for optimal power in a sample is not clear. Once a population-based sample has been collected, the incremental cost of adding an individual DNA sample to a pool is negligible. Through use of analytical derivation and optimisation, we provide robust guidelines for selecting pooling fractions. Our studies suggest that a symmetric sampling scheme of genotyping individuals from the 20-35% tails of the trait distribution is optimal under a variety of possible genetic models underlying the trait of interest. We also consider the effects of experimental errors from sources such as measurement and finite number of DNA templates on power to detect a QTL. Our studies suggest that an error of up to 1% in allele frequency estimation can be reasonably accommodated and finite number of templates in a pool is only problematic when the number of DNA templates is less than the number of individuals in a pool.


Jennifer K. Johnson1, Richard J. Viken2, and Richard J. Rose2
Genetic and environmental influences on the covariation between sensitivity and tolerance to alcohol3
1Department of Psychology, University of Southern California, Los Angeles, CA 2Department of Psychology, Indiana University, Bloomington, IN 3Supported by NIAAA 07611
Address: University of Southern California, Department of Psychology, 3620 S. McClintock Ave #501, Los Angeles, CA 90089-1061 Phone: 213 740 2255 Fax: 213 746 9082 Email: jennjohn@usc.edu

Changes in sensitivity to alcohol over time, also known as development of tolerance to alcohol, is a hallmark characteristic of alcohol dependence and has been nominated as a candidate for behavior genetic investigation. Selective breeding studies have shown that animals can be bred for both initial sensitivity and development of tolerance to alcohol (e.g. E.P. Riley and E.A Lochry, 1977, Drug and Alcohol Dependence 2, 485-494; M.B. Waller, W.J. McBride, L. Lumeng, and T.K. Li, 1983, Pharmacology, Biochemistry, and Behavior 19, 683-686). These results suggest that sensitivity and tolerance may, at least in part, be genetically influenced. Preliminary correlations for self-reported sensitivity and tolerance to alcohol showed substantial familiality and moderate heritability in a sample of approximately 150 twin and sibling pairs (J.K. Johnson, R.J. Viken, and R.J. Rose, 1999, Behav. Genet. 27, 596). The sample, now 300 pairs, will be subjected to model-fitting techniques to investigate the genetic and environmental influences on sensitivity, tolerance, and level of consumption. The multivariate relationships between these variables will be explored.


Wendy Johnson1, Matt McGue1, David Gaist2, James W. Vaupel2,3, and Kaare Christensen2
Heritability of Depression Symptomatology in the Second Half of Life: Evidence from Danish Twins over 454
1Department of Psychology, University of Minnesota, Minneapolis, MN, USA 55455 2Department of Psychology, Odense University, Odense, Denmark 3Max Planck Institute for Demographic Research, Germany 4Supported by National Institute on Aging Grant PO1-AG08761
Address: Department of Psychology, University of Minnesota, Elliott Hall, 75 East River Road, Minneapolis, Minnesota 55455 Phone: 612 625 4042 Fax: 612 626 2079 Email: john4350@tc.umn.edu

The heritability of depression symptoms was investigated in a sample of 2,169 pairs of Danish twins (1,033 MZ and 1,136 same sex DZ) ranging in age from 45 to over 95. Twins completed an interview assessment that identified symptoms of depression, which were scored on Affective, Somatic, and Total scales. For the full sample, heritability estimates (h2) for the Affective (h2 = .27), Somatic (h2 = .26), and Total (h2 = .29) scales were all moderate, statistically significant, and similar to results from other studies (e.g. McGue, M. and Christiansen, K., 1997, J. Abn. Psychol. 106, 439-448). To assess possible variations in heritability across the wide age span, the sample was stratified into age groups in increments of five years. Preliminary analyses suggest that the magnitude of heritable influence did not vary with age. Results of model fitting will be presented. The implications of these findings for understanding the symptomatology of depression in the second half of life will be discussed.


Toshimitsu Kamakura, Masaki Fujimoto, Hisako Itoi, Kunitake Suzuki, and Yuko Kobori
Genetic and environmental influences on self-esteem in a sample of middle-aged twin in Japanese
1Faculty of letters, University of Chiba 2 Faculty of Humanity, Tokyo Seitoku Univ.3Depertment of Psychology, Tokyo Gakugei University 4Graduate Course, Tokyo Metropolitan University 5Department of Psychology, Tokyo Gakugei University
Address: Hisako Itoi Depertment of Psychology, Tokyo Gakugei University Phone: +81 422 51 4458 Fax: +81 422 51 4458 Email: itoi@u-gakugei.ac.jp

Self-esteem in the psychological field is taken as a part of the self-concept and a feeling of self-evaluation. We apply Behavioral genetic analyses to the corresponding covariance data examining genetic and environmental influences on self-esteem in middle-aged Japanese twin. Behavioral genetic studies have focused on examining the genetic and environmental influences on self-concept and ego development. Some Behavioral genetic studies in the West showed that genetic factors moderately contribute to self-esteem. However, there have been few empirical attempts to investigate on the genetic and environmental influences on self-esteem using non-Western populations. Therefore, the purpose of the present study is to examine the mechanism of Japanese self-esteem in genetic and environmental influences using Japanese twin sample representing non-Western twin sample. Self-esteem is assessed by the 10-item Rosenberg Self-Esteem Scale (RSES) translated into Japanese. Subjects are asked to indicate the extent to which you think each item describes yourself. This measurement use a five-point Likert scale from strongly agree (5) to strongly disagree (1). We seek to explain the variations among by: (1) additive genetic factors (A); (2) environmental influences common to both twins (C, or Shared environment); and (3) environmental influences specific to each twin (E or nonshared environment) using ACE models. A discussion follows concerning the significance of difference cultural in the view of self-esteem.


Yong-Kyu Kim1
Drosophila Kin Recognition2
1Department of Genetics, University of Georgia, Athens, GA 2Supported by NSF grant (IBN-963-1801) to P. A. Gowaty and W. W. Anderson
Address: Department of Genetics, University of Georgia, Athens, GA 30602 Phone: 706 542 1448 Fax: 706 542 3910 Email: yongkyu@arches.uga.edu

Kin recognition significantly affects fitness (W. D. Hamilton, 1964, J. Theor. Biol. 7, 1-52; P. Bateson, 1983, in P. Bateson, ed., Mate Choice, Cambridge University Press) and is present in species possessing social systems where non-trivial probabilities of interactions among adult sibling exist. Drosophiladiscriminate between conspecifics and heterospecifics based upon courtship behavior using pheromones (E. B. Spiess, 1987, in D. J. C. Fletcher and C. D. Michener, eds., Kin Recognition in Animals, Wiley, New York; J. A. Coyne, A. P. Crittenden and K. Mah, 1997, Science 165, 1461-1464). Little is known, however, about kin recognition in Drosophila. Using the species complex Drosophila paulistorum, I observed courtship and mating behavior of flies raised in the following treatments: 1) siblings raised together communally; 2) siblings raised apart communally; 3) non-siblings raised together communally; and 4) non-siblings raised apart communally. When either siblings or non-siblings had been raised together, their sexual activities were significantly reduced (p<0.001), and they avoided mating with each other. Siblings discriminated between siblings and non-siblings, and preferred to mate with the non-siblings when given choices (p<0.01). Such results suggest that early association or familiarity reduces sexual attraction between individuals who have been raised together, as observed on humans (E. Westermarck, 1922, The History of Human Marriage, Allerton, New York; A. P. Wolf, 1995, Sexual Attraction and Childhood Association: A Chinese Brief for Edward Westermarck, Stanford University Press). Cuticular hydrocarbons may play a role in this sort of kin recognition in Drosophila.


Katherine M. Kirk1, and Nicholas G. Martin2
Longitudinal analysis of measures of anxiety and depression in adult twins
1Department of Psychiatry, University of Queensland and Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia 2Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia
Address: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Brisbane QLD 4029, Australia Phone: +61 7 3362 0278 Fax: +61 7 3362 0101 Email:kathE@qimr.edu.au

Additive genetic influences have previously been found to account for between 30% and 40% of the variance in anxiety and depression in adult twins residing in the general community. However, longitudinal data allows investigation into whether the same genetic influences are acting throughout adult life. Three separate Health and Lifestyle questionnaire-based studies conducted during a 15-year timespan each included measures of recent anxiety and depression, with a large proportion of twins in the overall sample participating in all three study phases. Longitudinal analysis of this data using simplex models indicates that the same additive genetic influences on anxiety and depression are acting on individuals in their 50s, 60s and 70s, with no evidence of additional "late-onset" genetic factors for either phenotype. However, only a small proportion (7-21%) of the non-shared environmental influences were found to be common across the timepoints considered.


Valerie S. Knopik1, Andrew C. Heath1, Pamela A. F. Madden1, Kathleen K. Bucholz1, Elliot C. Nelson1, and Nicholas G. Martin2
Genetics of Alcohol Dependence: Controlling for other heritable risk factors3
1Washington University School of Medicine, St. Louis, MO, USA 2QIMR, Brisbane, Australia 3Supported by NIH grants AA11998, AA10249, AA0758O, DA12854
Address: Valerie S. Knopik Washington University School of Medicine Department of Psychiatry 40 N. Kingshighway, Suite 1 St. Louis, MO 63108 USA Phone: 314 286 2299 Fax: 314 286 2213 Email: vsknopik@matlock.wustl.edu

In order to explore genetic risk factors for DSM-IV alcohol dependence in both men and women, diagnostic telephone interview data from young adult Australian twin pairs born 1964-1971 were analyzed using Cox regression and structural equation modeling techniques. Cox regression models were first fitted to interview data from a total of 2709 complete twin pairs (693 MZ female, 485 MZ male, 501 DZ female, 382 DZ male, and 648 DZ female/male pairs). Results of these analyses suggest that the risk for alcohol dependence is increased in males, in Roman Catholics, in those who report a history of major depression, panic disorder, and conduct disorder, or (in females only) a history of suicide attempt; whereas there is a decreased risk in those reporting Baptist, Methodist, or Orthodox religion, in males who report weekly church attendance, and in university-educated males. Structural equation models were subsequently fitted to the data to determine the extent of genetic and environmental influences on alcoholism liability while simultaneously controlling for effects of sociodemographic and psychiatric predictors on alcohol dependence liability. Results suggested that, after allowing for the effects of sociodemographic and psychiatric predictors, 49% of the total variance in alcoholism liability is attributable to additive genetic effects, 0% to shared environmental factors, and 51% to non-shared environmental influences, indicating a surprisingly high degree of specificity of genetic risk for alcohol dependence.


Kathryn S. Lemery, Nicole L. Schmidt, and H. Hill Goldsmith
Genetic and contrast effects on temperamental difficulty and unadaptability in infancy and early childhood
Waisman Center, University of Wisconsin-Madison, Madison, WI 53705
Address: Waisman Center; 1500 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 Phone: 608 265 4946 Fax: 608 263 0529 Email: klemery@facstaff.wisc.edu

Parent report of twin personality and temperament typically yields high heritability estimates with no shared environmental influences. However, the DZ correlations are often less than one half the MZ correlations, suggesting the presence of interactive genetic effects (dominance or epistasis) or twin contrast effects. Contrast effects, which may result from magnifying actual cotwin differences, are thought to be greater for DZ twins who show greater actual Behavioral differences. In a sample of 10-18 year olds, Saudino and colleagues (K. J. Saudino, S. McGuire, D. Reiss, E. M. Hetherington, and R. Plomin, 1995,J. Pers. Soc. Psych. 68, 723-733) found that once contrast effects were estimated, shared environmental influences were important for some dimensions of temperament. In the present study we interviewed the primary caregivers of over 1000 twin pairs using age-appropriate versions of Bates' Infant and Child Characteristics Questionnaires. Two factors were common to all versions: Difficulty, which is characterized by frequent and intense displays of negative emotion, and Unadaptability, or negative reactions to new people and new situations. Intraclass correlations suggested high heritability (Difficulty MZ R = .49, DZ R = .04; Unadaptability MZ R = .71, DZ R = .25). With Difficulty, there was some evidence of greater DZ variance (suggesting contrast), and the best fitting model included additive genetic, nonshared environmental, and sibling contrast effects, [chi]2 (12) = 9.68, p = .64, AIC = -14.32. On the other hand, there was no evidence of greater DZ variance for Unadaptability, and a model including interactive genetic effects but no contrast fit equally well, [chi]2 (12) = 4.01, p = .98, AIC = -19.99. Genetic and environmental effects were homogeneous across sex and age. Results suggest that contrast effects exist for some, but perhaps not all dimensions of temperament and discussion centers on distinguishing rating contrast effects from mutual sibling influences.


Jeffrey M. Lessem1, Stacey S. Cherny2, Goncalo R. Abecasis2, Pak C. Sham3, and Shaun Purcell3
An overview of regression methods of linkage analysis in selected samples4
1Institute for Behavioral Genetics, University of Colorado at Boulder 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom 3Social, Genetic and Developmental Research Centre, Institute of Psychiatry, Kings College, London, United Kingdom 4Supported by grants EY12562 and DA11015
Address: Institute for Behavioral Genetics, 447 UCB, Boulder, CO 80309-0447 Phone: 303 492 2843 Fax: 303 492 0852 Email: Jeff.Lessem@Colorado.EDU

The most convenient, rapid, and robust methods for analysis of linkage date are regression-based. Such methods include the Haseman-Elston (Haseman & Elston, 1972) and DeFries-Fulker (DeFries & Fulker, 1985) approaches and their extensions. The Haseman-Elston method is implemented in many common packages such as SAGE (Statistical Analysis for Genetic Epidemiology, Release 2.2) and Genehunter (Kruglyak et al, 1995), and therefore is often the first analysis performed by researchers. However it is not necessarily the most powerful method when analyzing a selected sample. The DeFries-Fulker regression approach and the Sham-Purcell (Sham & Purcell, 2001) extension to the Haseman-Elston method are particularly suited to analyzing data selected for the presence of an extreme proband. This study will use simulated data to determine the relative power achieved through the use of these different methods.


Christina N. Lessov1, Pamela A.F. Madden1, Kathleen K. Bucholz1, Wendy S. Slutske2, and Andrew C. Heath1
Toward characterization of adolescent nicotine dependence3
1Department of Psychiatry, Washington University School of Medicine, St. Louis MO 2Department of Psychology, University of Missouri, Columbia MO 3Supported by DA07261 and AA09022
Address: Department of Psychiatry, Washington University School of Medicine, 40 N. Kingshighway, Suite 1, St. Louis MO Phone: 314 286 2298 Fax: 314 286 2213 Email: christina@matlock.wustl.edu

The aim of this research is to understand the development of nicotine dependence in adolescents. We have initiated investigation into factors that influence ever trying smoking and transitions from smoking experimentation to nicotine dependence in a sample of adolescent female twins(Missouri Female Twin Study, MOAFTS; n=3418 individuals aged 12 to 23). Transitions were defined as a four-level variable of a) never smokers (55%), b) experimenters (27%), c) regular non-dependent smokers (8%), and d) regular dependent (DSM-IV criteria) smokers (10%). As previously shown (e.g. L. Chassin et al, 2000,Health Psychology 19, 223-231, K.P. Mayhew et al, 2000, Drug Alc. Dep. 59, S61-S81), having smoking peers or close friends who smoke was a significant risk for ever trying smoking (ORs=2.3-7.7), and was a progressively greater risk factor for transitioning from never smoking to each transition category (ORs=1.7-13.4). Adolescent report of parental smoking was not associated with ever trying smoking, in contrast to some reports (J.B. Unger and X. Chen, 1999,Addictive Behaviors 24, 371-381); maternal smoking history (never smoker versus experimented, ex-smoker, or current smoker) was a significant predictor only for transitioning to regular dependent smoking (ORs=2.1-2.7); co-twin's smoking history or having a boyfriend who is either current of ex-smoker, were significant predictors for both ever trying cigarettes and becoming a regular and dependent smoker (ORs=8.3-27.5 for co-twin status; ORs=2.1-8.3 for boyfriend status). Correcting for the effects of age did not alter the significance of any of the predictors. Genetic analyses showed modest heritability (19%) and considerable shared environmental influences (71%) on ever trying smoking. Preliminary univariate genetic analyses suggested a progressive increase in the importance of genetic factors (18% to 75%) in transitioning from smoking experimentation to regular dependent smoking. These results indicate that different factors and differential genetic influences affect different stages of adolescent development of nicotine dependence.


Florence Levy1, David A. Hay2, Michael McStephen2,3, and Nicholas G. Martin4
Intergenerational Transmission of ADHD and Associated Psychopathologies
1School of Psychiatry, University of New South Wales, Sydney, NSW, Australia 2School of Psychology, Curtin University of Technology, Perth, Western Australia, Australia 3 Mental Health Research Institute of Victoria, Melbourne, Victoria, Australia 4 Queensland Institute of Medical Research, Brisbane, Australia 5Supported by the NHMRC (Australia)
Address: Avoca Clinic, Royal South Sydney Hospital, ZETLAND 2017, NSW, Australia Phone: +61 2 9382 8213 Fax: +61 2 9382 8105 Email: F.Levy@UNSW.edu.au

The subtype specificity of ADHD subtypes in affected sibling pair (ASP) families has been questioned by Smalley et al (S. L. Smalley, J.J. McGough, M. Del Homme et al., 2000, J. Am. Acad. Child Adol. Psychiatry 39, 1135-1143). The authors found no evidence that affected siblings or parents within ADHD families showed similar patterns of ADHD symptoms such as subtype classification. In contrast, our group has found that only 6% of MZ twins compared with 25% of DZ twins had different DSM-IV subtypes (Hay et al., in preparation).The present study examines ADHD subtype specificity in 649 families, from a sample of adult twins and their children where parents had completed DSM-IV based questionnaires about themselves and their children. There were 12 families in which one parent had the Inattentive subtype, 29 families in which one had the Hyperactive/Impulsive subtype and 15 families in which one parent had the combined subtype. When the children in these families are examined, 3/12 children born to couples where one has Inattention, also had Inattention; only 1/29 born to a couple where one had Hyperactivity/Impulsivity also had Hyperactivity/Impulsivity and 2/15 children born in a family where one had the Combined type also had that type. On the other hand a total of 129 children met criteria for a subtype of ADHD (84 Inattention, 23 Hyperactivity-Impulsivity and 22 Combined). These data support the Smalley et al findings of a lack of subtype specificity in families. Reasons for differences in twin and family data are discussed.


Paul Lichtenstein1, and Peter Annas2
Shared environmental effects are important for stability and genetic effects for change in fears and phobias from in the transition childhood to early adolescence
1Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden 2Department of Psychology, Uppsala University, Uppsala, Sweden
Address: Box 281, SE-171 77 Stockholm Phone: +46 8 728 7424 Fax: +46 8 314 975 Email: paul.lichtenstein@mep.ki.se

Fears and phobias are common among children and these traits tend to run in families. Cross-sectional studies suggest that both genetic and shared environmental effects are responsible for the familiality for fears and phobias; but it is not known how genetic and environmental influences contribute to change and stability in the transition from childhood to early adolescence. In a sample of 1,500 Swedish twins first contacted when they were 8-9 years old and followed up when they were 13-14 years old, we found that both genetic and shared environmental effects are of importance at both ages. While shared environmental effects contribute to stability, different genetic effects are important at the two time points. Fears have been shown to be relatively transient in childhood, and this study indicates that this is partly because different genetic influences are operating over time. Shared environments contribute to stability throughout childhood.


Hiroko Maekawa1, Juko Ando1, and Yutaka Ono2
Genetic and environmental relationships between eating disorder and personality in the Japanese female twin sample
1Faculty of Letters, Keio University 2Department of Neuropsychiatry, School of Medicine, Keio University
Address: 5-19-9-304,Nishikamata,Ota-ku,Tokyo,144-0051,Japan Phone: +813 3734 5125 Fax: +813 3734 5125 Email:hm-hiro@pop21.odn.ne.jp

In this study, genetic and environmental relationships between eating disorder and personality were investigated with 53(17-27 years old) Japanese female twins. The investigations were carried out in the successive two years; the NEO-PI-R and the Temperament and Character Inventory (TCI) in the first year and the Eating Disorders Inventory (EDI) in the second. In the EDI scales, CE model fitted best for Drive for thinness and Bulimia. The shared contributions of Drive for thinness and Bulimia were 42% and 33% ,respectively. On the other hand, AE model fitted best for Body dissatisfaction, and the genetic contribution was 68%. For the relationship between EDI scales and Personality, Neuroticism and Harm Avoidance affected Drive for thinness and Bulimia. Multivariate analysis revealed that trait-specific shared environmental and common environmental factors affected personality and EDI scales respectively.


Hermine H. Maes1, Andrew C. Heath2, Nicholas G. Martin3, Michael C. Neale1, and Lindon J. Eaves1
Genetic and environmental influences on smoking initiation. An extended twin kinship analysis4
1 Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond VA 23298 2Department of Psychiatry, Washington University, St. Louis, MI 63108 3Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia 4 Supported by NIH grants AG04954, GM30250, GM32732, AA06781, AA07728, AA07535, MH40828, NH&MRC941177, Nabisco, Templeton, HL60688, MH45268, MH01458, MH57761
Address: VIPBG, MCV/VCU, P.O. Box 980003, Richmond VA 23298-0003 Phone: 804 828 8145 Fax: 804 828 8801 Email: hmaes@hsc.vcu.edu Web: http://www.vipbg.vcu.edu

Previous analyses of the twin data on smoking initiation from the Virginia 30,000 indicated that additive genetic factors accounted for 49-64%, shared environmental factors for 19-29% and specific environmental factors for 16-22% of the individual differences (Heath et al., 1993, J. Subst. Abuse 5, 221-246). We re-analyzed the data including the extended kinship data on the parents, siblings, spouses and children of the twins. Smoking initiation (ever having smoked) was regressed on age, sex, twin status and sample and their interactions. The Stealth model of family resemblance (Eaves et al, 1999, Proceedings of 1994 APPA Conference 269-308) was fitted to the normalized residuals using Mx. The full model allows testing for additive and dominant genetic effects, shared and unique environmental effects, special twin environment, phenotypic assortative mating, vertical cultural transmission, and genotype-environment correlation, including complete testing for sex differences (both in magnitude and effect). Results indicate that genetic factors (sum of additive and dominance effects) account for 40% of the variance in males and 27% in females. Shared environmental effects contributed 25% and 33% in males and females respectively. These effects consist of non- parental shared environment (15-19%), special twin environment (9-14%), and non-significant cultural transmission effects. These results support the greater importance of shared environmental factors in the initiation of smoking in women compared to men.


Holly A. Mack1,2, Michael D. Grant1,2, Tara K. Kerin1,2, Jose R. Fernandez3, George P. Vogler1,2, David J. Vandenbergh1,2, and Gerald E. McClearn1,2
Quantitative Trait Loci (QTL) Analysis of Body Weight in F2 and Recombinant Inbred Mice4
1Department of BioBehavioral Health, The Pennsylvania State University, University Park, PA 2 Center for Developmental and Health, The Pennsylvania State University, University Park, PA 3 New York Obesity Research Center; St. Luke's/Roosevelt Hospital Center, Columbia University, New York, NY 4 Supported by NIA Grant AG00276 & AG14731, NIAAA Grant AA08125
Address: Center for Developmental and Health Genetics, 101 Amy Gardner House, The Pennsylvania State University, University Park, PA 16802 Phone: 814 865 1717 Fax: 814 863 4768 Email: ham113@psu.edu

Obesity is a major health concern and a known risk factor for cardiovascular disease, stroke, and diabetes. Approximately 55% of adults in the United States are clinically overweight. Previous research has shown that numerous genes influence body weight and obesity with each individual locus contributing a moderate, varying effect to the overall phenotype (D. Pomp, 1997, Behav. Genet 27, 285-306). It has been reported that these loci affecting body weight and growth change with age (J. M. Cheverud, E. J., Routman, F. A. M. Duarte, B. van Swinderen, K. Cothran, & C. Perel, 1996, Genetics 142, 1305-1319). Research focusing on quantitative trait loci (QTLs) associated with body weight proves efficacious in studying health-related problems associated with obesity. The present study utilized two F2 samples and two recombinant inbred (RI) samples derived from C57BL/6 and DBA/2 strains to nominate putative QTLs for body weight. Body weight was assessed at 60 days of age for one of the F2 and RI samples, and at 150 days for the other F2 and RI samples. Analyses were performed with combined sexes and sexes separately using genetic linkage analysis, regression, and correlation analysis. Results for all four samples show significant QTL regions for body weight. Developmental stages, sex differences, and possible candidate genes will be discussed.


Neilson C. Martin, Goncalo R. Abecasis, and Lon R. Cardon
Assessment of Stratification in Linkage and Association Samples
Wellcome Trust Centre for Human Genetics, Oxford
Address: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN E-mail: neilson.martin@well.ox.ac.uk Web: http://www.well.ox.ac.uk/bioinformatics

Population stratification is often cited as a primary contributor of inflated false positive rates in genetic association studies. As a result, a number of robust family-based association strategies have been devised. These methods can protect against inflated Type I error due to sample mixing, but are also very inefficient in their usage of genotype data. An alternative to this strategy has been developed in the form of 'genomic control' (J.K. Pritchard and N.A. Rosenberg, 1999, Am. J. Hum. Genet. 65, 220-228; S.A. Bacanu, B. Devlin, and K. Roeder, 2000, Am. J. Hum. Genet. 66, 1933-1944) in which anonymous genetic markers are used to assess the background degree of stratification and control for it when it is present. Here we apply the method of Pritchard and Rosenberg to publicly available genome-screen data sets to evaluate the level of stratification in existing samples. The CEPH collection provides an illustrative example for these analyses, comprising more than 30 families that have been genotyped on up to 9,000 genetic markers. Random selection of a set of 40 unlinked markers was conducted 5000 times to evaluate the test statistic distribution. The results indicate a high level of homogeneity in the Utah samples, but increasing heterogeneity in the total sample on addition of the French, Amish and Venezuelan collections. These outcomes show promising sensitivity in the stratification test as a global indicator of sample heterogeneity.


Andrew J. Birley1, Michael C. Neale2, Katherine M. Kirk2 and Nicholas G. Martin1
Anxious genes and the EDAC design
1Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia 2Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA
Address: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Brisbane QLD 4029, Australia Phone: +61 7 3362 0278 Fax: +61 7 3362 0101 Email:andrewBi@qimr.edu.au

Human anxiety, depression and neuroticism are all about 50% heritable and their inheritance is best described by a common latent genetic factor. The extreme discordant and concordant (EDAC) design, promises to be an efficient approach to the detection of linkage for such quantitative characters. This strongly contrasts with the effects of non-shared or unique sibling environmental variation, where most of the variation is specific to the individual phenotypes. Multivariate structural equation models for neuroticism and related phenotypes have provided evidence for QTL's. A "Weighted Likelihood Model" has been used to detect QTL's in which the expected contributions of the variance due to a QTL, residual polygenic and environmental variance are modelled in accordance with their contribution to the three possible configurations of identity-by-descent for sib pairs. After statistical moderation of the results to accommodate for multiple comparisons, the 10cM genome scan provided evidence for several linkages. Remarkably one linkage conformed to Gray's dimensions of Anxiety and Cloninger's dimensions for Harm Avoidance. Whilst replication of these findings in other populations will be an essential part of any strategy designed to find genes for anxiety and depression by linkage and positional cloning, this application of the EDAC design is encouraging.


Jeanne McCaffery1, Raymond Niaura1, John Todaro1, Dorit Carmelli2, and Gary Swan2
The association between depressive symptoms and common variance among metabolic risk factors for cardiovascular disease: results from the NHLBI twin study
1Department of Psychiatry, Brown University Medical School, Providence, RI 2SRI, International, Menlo Park, CA
Address: 148 Shaw Ave., Cranston, RI 02905 Phone: 401 467 3449 Email: Jeanne_McCaffery@brown.edu

Recent evidence suggests that depression predicts early cardiovascular morbidity and mortality. Furthermore, it has been hypothesized that depression is associated with an accumulation of metabolic risk factors for cardiovascular disease (CVD), suggesting one mechanism through which depression may affect cardiovascular outcomes. In this study, we characterize covariation among systolic and diastolic blood pressure, body mass, waist-to-hip ratio, and fasting triglycerides and glucose in terms of principle factors and determine whether any association between depressive symptoms, as indexed by the Center for Epidemiological Studies – Depression Scale (CES-D), and the resultant factors is genetic or environmental in origin. Participants were 87 monozygotic and 86 dizygotic Caucasian male twin pairs (ages 59-69) who served in World War II. Persons self-identifying as diabetic were excluded. Factor analysis with oblimin rotation (allowing for covariation among factors) y! ielded two factors. Each of the component variables loaded onto the first factor, whereas systolic and diastolic blood pressure loaded mostly highly on the second. Univariate twin structural equation modeling indicated that the factors were each primarily attributable to genetic (a2= .55, .45, respectively, p’s < .05) and nonshared environmental effects (e2= .45, .55, respectively, p’s < .01) with little or no contribution of shared environment (p’s >.10). CES-D scores were primarily influenced by nonshared environment at the univariate level (e2= .75, p < .01; a2 and c2, p’s >.10) and correlated modestly with both of the phenotypic factors (r’s = .18, .13, respectively, p’s < .05). Bivariate twin modeling suggested that common nonshared environmental effects accounted for the association between depressive symptoms and factor 1 and 2 (ere >80%; re = .25, .24, respectively, p’s < .05). These results indicate that depressive symptoms are associated with the common variance among risk factors for CVD for environmental reasons that are independent of genetic effects, suggesting that depressive symptoms may, in part, be an environmental risk factor for CVD.


Matt McGue1, and William G. Iacono1
The nature of shared environmental influence on adolescent Behavioral deviance: Parent versus sibling effects2
1Department of Psychology, University of Minnesota, Minneapolis MN 2Supported by NIH Grant AA11886
Address: Department of Psychology, 75 East River Road, Minneapolis MN USA 55455 Phone: 612 625 8305 Fax: 612 626 2079 Email: mcgue001@tc.umn.edu

Adolescent Behavioral deviance, including delinquency and substance use and abuse, appears to be an exception to the general observation that shared environmental influences on psychological characteristics are trivial or nonexistent. The specific factors that contribute to the shared environmental influence on adolescent deviance have, however, remained illusive. Traditional socialization theories emphasize the importance of parental influences, although the research supporting these theories is typically based on the study of intact nuclear families where genetic and shared environmental influences are confounded. Alternatively, Rowe & Gulley (1992, Criminology 30, 217-233) and McGue, Sharma & Benson (1996, J. Stud. Alc. 57, 8-18) using Behavioral genetic approaches have argued that sibling factors are a much more potent source of familial environmental influence on adolescent deviance than parental factors. In 1998 we initiated the Sibling Interaction and Behavior Study (SIBS) in order to explore the differential influence of parents and siblings on adolescent Behavioral deviance. The SIBS sample will ultimately consists of 400 adoptive and 200 biological families, each of which consists of a pair of adolescent siblings and their parents. The SIBS assessment is extensive and consists of in-person clinical interviews, self-report and videotaped assessment of family functioning, and measures of personality, cognitive ability, and academic achievement. Preliminary results from the first 180 adoptive and 60 non-adoptive families will be presented. The focus of the findings presented will be adolescent use of tobacco, alcohol, and illicit substances.


Michael McStephen1,2, David A. Hay1, and Florence Levy3
Modelling the relationship of Inattention and Hyperactivity/Impulsivity in ADHD 4
1School of Psychology, Curtin University, Western Australia, Australia 2 Mental Health Research Institute of Victoria, Parkville, Victoria, Australia 3Department of Psychiatry, University of New South Wales, Sydney, NSW, Australia 4Supported by the NHMRC (Australia)
Address: Mental Health Research Institute of Victoria, Locked Bag 11, PARKVILLE 3052, Australia Phone: +61 3 9389 2931 Fax: +61 3 9387 5061 Email: M.McStephen@papyrus.mhri.edu.au

Quantitative genetic modelling was posed a major challenge when DSM-IV recognised three subtypes of ADHD, the Inattentive, the Hyperactive/Impulsive and the Combined type with both Inattentive and Hyperactive/Impulsive symptoms. Any routine multivariate model of the covariance between the two groups of symptoms cannot explain (1) the high prevalence of the Combined subtype relative to the Hyperactive/Impulsive subtype (2) the twin studies which indicate the relative genetic independence of the three subtypes and (3) the differential and distinct associations of the three subtypes with such comorbid conditions as speech and reading difficulties, Conduct Disorder and Developmental Co-ordination Disorder (Piek, J.P., Pitcher, T.M. and Hay, D.A. (1999). Dev Med Child Neurol 41, 159-165). The model that Neale and Kendler (Neale Michael C, and Kendler Kenneth S (1995). Am J Hum Gen 57, 935-953) developed to explore the comorbidity of Generalised Anxiety and Major Depressive Disorders can be applied to the relationship between Inattention and Hyperactivity/Impulsivity symptoms and the three DSM-IV subtypes. It was possible to reject the most obvious model of Inattention and Hyperactivity/Impulsivity as independent liabilities. Somewhat better than the model of three independent disorders, was the random multiformity model and its explanation of the distribution of Hyperactive/Impulsive symptoms in the Inattentive subtype and vice versa. This model has significant implications for both molecular genetic and neuropsychological approaches that focus on features of Inattention and Hyperactivity/Impulsivity.


Jonathan S. Mill1, Joseph L. McClay1, Karen Sugden1, Philip J. Asherson1, Richie Poulton2, Terrie E. Moffitt1, and Avshalom Caspi1
DRD4, psychopathology, and personality: preliminary findings from the Dunedin multidisciplinary health and development study
1SGDP Research Centre, Institute of Psychiatry, De Crespigny Park, London, England. SE5 8AF 2Otago University Medical School, Dunedin, New Zealand
Address: SGDP Molecular Genetics Laboratory, Institute of Psychiatry, De Crespigny Park, London, England. SE5 8AF Phone:+44 20 78480396 Email: j.mill@iop.kcl.ac.uk

The 7-repeat allele of the DRD4 exon-3 VNTR (DRD4*7) is one of the most intensely studied polymorphisms in genetic studies of behavioural phenotypes. Associations with a wide range of personality traits and psychopathologies have been postulated, and in particular the association with ADHD is widely believed to be one of the strongest findings in psychiatric genetics. Although considerable work has been done on DRD4 in small clinical samples, the relationship between the alleles of this gene and quantitative measures of behaviour in a large population-based sample have never been studied. We have genotyped the majority of participants in the Dunedin multidisciplinary health and development study, a 26-year longitudinal study of a phenotypically well-characterised birth cohort (N=1037), and carried out preliminary analysis on the data. Initial findings seem to play down the role of DRD4*7 in hyperactivity, but support an association with quantitative and categorical measures of alcoholism, as well as negative emotionality personality traits.


Brian S. Mustanski1, Richard J. Viken1, Jaakko Kaprio2, Lea Pulkkinen3, and Richard J. Rose1
Genetic and Environmental Influences on Pubertal Development in Males and Females
1Department of Psychology, Indiana University 2Department of Public Health, University of Helsinki, Finland 3Department of Psychology, University of Jyv„skyl„, Finland FinnTwin12 has been supported by NIAA (AA09203) and the Academy of Finland
Address: Indiana University Department of Psychology, Bloomington, IN 47404 Email: bmustans@indiana.edu Webpage: http://php.indiana.edu/~bmustans

The relationship of pubertal changes to Behavioral, emotional, and social functioning illustrates the utility of a biopsychosocial model of adolescent development (Compas, Hinden & Gerhardt, 1995, Ann. Rev. Psychol. 45, 265-293). The impact of pubertal changes on relationships to parents and peers and the replicated associations of early-onset puberty to depression and anxiety, precocious sexual behavior, externalizing Behavioral problems, eating disorders, and early substance use (Dick, Rose, Viken & Kaprio, 2000, Developmental Psychology 36, 180-189) have received much attention in the adolescent research literature and have identified a number of factors that impinge on pubertal timing, including family structure, father absence, maternal timing, stress and nutrition. Understanding how these factors influence pubertal timing is restricted by limited knowledge of the underlying genetic architecture. We explore these issues in a population-based sample (N= 1936 pairs) of Finnish twins (FinnTwin12). At ages 11-12 and 14, each twin reports on the status of five pubertal development characteristics, comprising the Pubertal Development Scale (Petersen, Tobin-Richards, & Boxer, 1983, J. Early Adolescence 3, 47-62). Sex limitation models, which exploit data from opposite sex DZ twins, were fit to the data. Significant additive genetic effects for pubertal timing in males and females were found at both 12 and 14. A significant common environmental effect was found for females at age 12, and for both males and females at age 14. These models implicate different genetic factors in the timing of puberty in males and females. Additionally, multivariate models where fit to the data to explore the commonality of various facets of pubertal development, as well as gender difference in timing. Results of these models will be presented in order to help characterize the underlying genetic architecture of pubertal development in males and females.


Marcus Munafo1, Robert Walton, Elaine Johnstone1, Patricia Yudkin2, Michael Murphy, Lindsay Stead1, and Lon Cardon3
The Genetic Basis for Tobacco Dependence: A systematic review
1 Imperial Cancer Research Fund General Practice Research Group, University of Oxford 2 Department of Primary Health Care, University of Oxford 3 Wellcome Trust Centre for Human Genetics, University of Oxford
Address: ICRF GPRG, Institute of Health Sciences, University of Oxford, Old Road, Oxford OX3 7LF Phone: +44 1865 226756 Fax: +44 1865 227137 Email: marcus.munafo@dphpc.ox.ac.uk

There is strong evidence from twin studies for a genetic component to the development and maintenance of tobacco addiction, but the precise contribution of individual genes is uncertain. We undertook a meta-analysis of existing evidence on the relationship between genetic polymorphisms and smoking behaviour to quantify genetic effects and inform future research. We sought to identify all published observational studies linking genetic variants to any aspect of smoking behaviour. Data were extracted from papers independently by two reviewers using standard forms. Effect sizes attributable to the polymorphisms (calculated as relative risks and standardised mean differences) were combined where appropriate using a fixed effects model. Nineteen studies on 9 genes met inclusion criteria. The genes studied coded for: dopamine receptors D1, D2 and D4; dopamine transporter; cytochromes P450 2D6, 2A6, 1A1; tyrosine hydroxylase; serotonin transporter. Adopting the smoking habit was linked to possession of the DRD2 A1 polymorphism (Relative risk 1.37; 95% CI 1.10, 1.76). The data suggest a dominant mode of action for the DRD2 A1 polymorphism. Persistent smoking behaviour was more common in those with the DRD2 A1 polymorphism (RR 1.45; 95% CI 1.51, 2.15) and less common with the DAT 1, 9 repeat allele (RR 0.87; 95% CI 0.78, 0.95). The DAT 1, 9 repeat allele was less common in those who had successfully stopped smoking (RR 0.81; 95% CI 0.67,0.97). Level of cigarette consumption in smokers was higher in people with: DRD2 A1 (standardised mean difference 0.95; 95% CI 0.55, 1.35); cytochrome P450 1A1 Msp I (SMD 0.36; 95% CI 0.02, 0.69); serotonin transporter L allele (SMD 0.54; 95% CI 0.25, 0.84). This review confirms significant effects of two genetic polymorphisms on smoking behaviour and highlights their public health impact. DRD2 A1 is present in 29% of Caucasians and may account for 2.4 million smokers in the United Kingdom. Fifty-one percent of Caucasians lack the protective DAT1, 9 repeat allele accounting for 1.2 million smokers in the UK. Larger studies will be needed to assess the effects of homozygosity (particularly for cytochrome P450 enzymes) and combinations of alleles and to evaluate implications of genetic variation for prevention and treatment of tobacco dependence.


Kazuko Nakashima1, and Kanehisa Morimoto1
Studies of Chromosome Sensitivities in Twin Children
1Osaka University Graduate School of Medicine, Social and Environmental Health
Address: Osaka University Graduate School of Medicine, Social and Environmental Health F1 2-2, Yamada-oka, Suita, Osaka 565-0871, JAPAN Phone: +81 6 6879 3923 Fax: +81 6 6879 3923 Email: pon@envi.med.osaka-u.ac.jp

To elucidate the contribution of genetic factors in determining chromosomal sensitivity to genotoxicant exposure in healthy persons, we have investigated chromosome damage in lymphocytes from monozygotic (MZ) and dizygotic (DZ) twins. Whole blood was drawn from monozygotic (pairs; male, 5 and female, 8) or dizygotic (pairs; male, 3) twins (aged 11-12 years old) and their mothers. Macro cultures have been done for each sample for 52 hr for the chromosomal aberration (CA) analysis, and for 72 hr with bromodeoxyuridine (40 micro M) for the sister chromatid exchange (SCE) analysis (K. Morimoto, M. Sato-Mizuno and A. Koizumi, 1985, Mutat. Res. 152, 187-196). The cells for CA analysis were also exposed to gamma-rays (2 Gy; dose rate, 0.5 Gy/hr) only or gamma-rays and cytosine arabinoside (ara-C; 5*10-5M) simultaneously at G0phase. The cells for SCE analysis were also treated with mitomycin-C (MMC; 3*10-8M) or 4-nitroquinoline 1-oxide (4NQO; 40ng/ml) for the entire culture (K. Iijima and K. Morimoto, 1991, Mutat. Res. 263, 263-268). The frequencies of the dicentric and ring (D+R) frequencies in cells exposed to gamma-rays only or gamma-rays plus ara-C showed no significant difference regarding to the zygosity. The SCE frequencies in non-treated, or MMC- or 4NQO-treated cultures also showed no difference regarding to the zygosity. Snedecor and Chochran's inter-class correlation coefficients between twin children showed no consistent tendency. SCE frequencies between twin children and their mothers showed no difference in zygosity. We investigate the frequencies of chemically induced SCEs or radiation-induced chromosome aberrations in lymphocytes drawn from twin children, and compared intraclass correlation coefficients between MZ and DZ twins. Analysis of baseline and mitomycin-C-induced SCEs and radiation-induced chromosome aberrations revealed that intraclass correlation coefficients were significantly higher for MMC-induced SCE frequencies among MZ.


Donald J. Nash1, Alan Schell2, Brooke Quigley3, Jake Adams4, and Bryan Hill5
Sensory deprivation and predatory behavior in mice
Department of Biology, Colorado State University, Fort Collins, CO
Address: Department of Biology, Colorado State University, Fort Collins, CO 80523 Phone:970 491 5481Fax: 970 491 0649 Email: dnash@lamar.colostate.edu

The microphthalmic white gene (Miwh) is an allele at the mi locus in chromosome 6. Homozygotes are all white and their eyes, which appear pinkish, are slightly microphtyalmic. Cataracts frequently are present. Unlike mi/mi homozygotes, Miwh/Miwhmice have abnormal skeleton. Miwh/+ mice show a diluted coat color and typically have large belly spots. Both homozygotes and heterozygotes show severe abnormalities of the inner ear in both the cochlear and vestibular positions and hearing is severely impaired. Miwh/+ mice, and, to a lesser extent, Miwh/Miwhmice, show an increased susceptibility to audiogenic seizures. The present study was designed to examine effects of senory deprivation on predatory behavior. Male and female mice of a congenic strain segregation for the Miwhgene were tested for their ability to catch and eat a cricket. Mice were tested on two consecutive days. In general, the homozygous Miwh/Miwhmice were less effective in capturing crickets than were the heterozygous or normal mice and were successful only half as often and did not show as much improvement in time with successive trials. Although the Miwh/Miwhhave severe deficits in hearing and vision, they do not appear to be severely handicapped in capturing prey.


Michael C. Neale1, and Kenneth S. Kendler1
The analysis and statistical power of data collected from screened samples of twins2
1 Virginia Institute for Psychiatric & Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond VA 23298 2 Supported by NIH grants RR-08123 and MH-01458
Address: VIPBG, MCV/VCU, P.O. Box 980126, Richmond VA 23298-0126 Phone: 804 828 3369 Fax: 804 828 1471 Email: neale@hsc.vcu.edu Web: http://www.vipbg.vcu.edu

Analyses have shown that classical twin studies of disorders with low population prevalences, e.g., less than five percent, are hampered by low statistical power (M.C. Neale, L.J. Eaves & K.S. Kendler, 1994 Behav Genet 24, 239-258). The large samples of twins required to obtain parameter estimates that are reasonably accurate become prohibitive when the phenotypic assessment of the disorder is expensive, such as psychiatric interview or laboratory assessment. One way to increase power is to use an inexpensive screening instrument to obtain a selected sample in which at least one twin screens positive, and to follow these pairs up with the more expensive assessment. Analysis of these selected samples is not always straightforward. In theory, joint maximum likelihood analysis of the screen and the diagnosis will provide unbiased estimates because the diagnoses are missing at random, conditional on the screening instrument score (R. J. A. Little & D. B. Rubin, 1987, Statistical Analysis with Missing Data, Wiley and Son, New York). However, this theory does not hold when both the screen and the diagnosis are binary variables, and it becomes necessary to correct for ascertainment. We consider the study cost as a function of: sampling a proportion of the pairs in which both members screen negative; analyzing the screen or diagnosis as a polychotomous instead of binary variable; the screen and diagnosis thresholds; and the underlying genetic model describing the variation within and covariation between the screen and the diagnosis.


Michelle B. Neiss1, Elizabeth F. Gramzow1, Constantine Sedikides1, and Jim Stevenson.1
Multivariate analysis of level and lability of self-esteem
1Department of Psychology, University of Southampton, Southampton SO17 1RE, UK
Address: Department of Psychology, Highfield Campus, University of Southampton, Southampton SO17 1RE, UK Phone: +44 23 8059 4584 Fax: +44 23 8059 4597 Email: mbn@soton.ac.uk

Although previous Behavioral genetic studies of self-esteem have examined long-term stability in self-esteem (S. McGuire, B. Manke, K.J. Saudino, D. Reiss, E.M. Hetherington, & R. Plomin, 1999, Child Development 70, 1283-1296), little research has focused on lability of self-esteem. Lability of self-esteem may be related to other personality dimensions such as emotionality or neuroticism. It is therefore of interest to determine the extent to which level and lability are distinct at the phenotypic level. The question then arises as to the extent to which the same or independent genetic and environmental influences affect level and lability of self-esteem. The current study builds upon previous research by presenting a Behavioral genetic analysis of the relationship between level and lability of self-esteem. Participants (N=251 pairs) drawn from the Register of Child Twins provided information on global self- esteem, domain-specific self-concept, and lability in self-esteem. We used a Cholesky decomposition to investigate genetic and environmental contributions to both level of self-esteem and lability of self-esteem. Substantial portions of the variance in both level and lability of self-esteem were attributable to genetic and non-shared environmental influences; no shared environmental influences were found. Approximately half of the genetic variance and two-thirds of the non-shared environmental variance in lability of self-esteem were specific to lability rather than in common with level of self-esteem.


Jenae M. Neiderhiser1, and Alison Pike2
Does Parenting Really Matter? A Test of the Nurture Assumption3
1Center for Family Research, George Washington University, Washington, DC 20037 2Department of Psychology, University of Sussex 3Supported by NIH Grants MH43373 and MH48825 and the William T. Grant Foundation
Address: Center for Family Research, George Washington University, 2300 Eye St., N.W., Room 613 Ross Hall, Washington, DC 20037 Phone: 202 994 2212 Fax: 202 994 4812 E-mail: cfrjmn@gwumc.edu

A new debate has begun on the importance of parents vs. peers to the development and socialization of children. A theory promoted by Harris (J.R. Harris, 1995, Psych. Rev. 102, 458-489) proposes that children's peers are the primary factor in influencing the way children behave while traditional socialization researchers have asserted that parents are the primary socializing influence on children (W.A. Collins, E.E. Maccoby, L. Steinberg, E.M. Hetherington, M.H. Bornstein, Marc H., 2000, Am. Psychologist 55, 218-232). Although both sides in this debate have used evidence from behavioral genetic research to bolster their case, there has not yet been a systematic examination of the peer socialization theory using a genetically sensitive design. This paper will examine this theory in the Nonshared Environment in Adolescent Development project (NEAD) as study of 395 families examined longitudinally. The NEAD assessed parenting and adolescent adjustment using multiple reporters and observer ratings and peer characteristics using parent and child reports. We found evidence that the parent-child relationship mediated the association between peer group characteristics and child adjustment and that these associations could be explained by mostly genetic factors. The remaining association between peers and adolescent adjustment was also due to primarily genetic factors suggesting that the adolescents have an active role in selecting their peers. These findings suggest that although peers are important in influencing adolescent adjustment, relationships with parents also play a critical role. Finally, finding that genetic factors are important underscores the role of the adolescent in determining how these two socializing forces affect their adjustment.


Naoko Onoda1,Juko Ando2, and Yutaka Ono1
A Longitudinal Study of Japanese Adolenscents' Depression and Parenting They Received
1Department of Neuropsychiatry, Keio University School of Medicine 2Department of Education,Faculty of Letters, Keio University
Address: Department of Neuropsychiatry,Keio University 35 Shinanomachi Shinjuku Tokyo Phone: +813 3353 1211 (62453) Fax:+81 3 5379 0187 Email: naoko-o@med.keio.ac.jp

In this study, a longitudinal twin design was used to clarify the etiology of depression and relationship between parenting received in childhood. 38 same-sex twin pairs completed Hospital Anxiety and Depression Scale(HADS) twice, approximately 2 or 3 years apart. At time 1, they completed Parental Bonding Instrument(PBI) also. Genetic correlation between depressive mood at time 1 and 2 is more than 0.9, and genetic correlation between depressive mood at time 1 and maternal parenting twins received (i.e. affectionless control) is more than 0.6. But genetic relationship between time 2 and maternal affectionless control is not so strong, correlation is about 0.3. On the other hand for paternal affectionless control there is no genetic relationship between depressive mood either time1 or time 2 (correlation is 0.06 and -0.05). It is suggested that genetic trait of eliciting affectionless controlling parenting from mother has much influence on depression.


George D. Papandonatos1, Richard Rende2, Ray Niaura2, and Elizabeth E. Lloyd2
Smoking Progression Among Adolescents: A sibling study3
1Center for Statistical Sciences, Brown University, Providence, RI 02912 2Brown-Lifespan Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI 02906 3Supported by NCI/NIDA grant P50CA84719 and NIMH grant MH01559
Address: Center for Statistical Sciences, Brown University, Box G-H, Providence, RI 02912 Phone: 401 863 9186 Fax: 401 863 9182 Email: gdp@stat.brown.edu

Utilizing the genetic subsample from the first two waves of the Add Health dataset (P.S. Berman, J. Jones and J.R. Udry, 1997,The National Longitudinal Study of Adolescent Health: Research Design), we employed 2nd order Generalized Estimating Equation methodology (P.J. Heagerty and S. Zeger, 1996, J. Amer. Stat. Assoc. 93, 150-162) to examine the longitudinal progression of smoking, defined in discrete stages (Never Smokers, Experimenters, Intermittent, Regular/Established), among 2199 adolescent sib pairs (256 MZ, 405 DZ, 929 FS, 328 HS, 281 NR) as a function of sib-pair type, alcohol use, social-environmental influences (cigarette availability, peer and parental cigarette use) and demographics (race/ethnicity, age and gender). By using a partial-proportional odds model for the mean structure we were able to estimate stage-specific influences of the covariates of interest, while an additional regression model for the log-odds ratios allowed us to model both the within- and cross-sib associations as a function of sib-pair type, age and gender composition and to test for sib-type differences. This flexible modeling framework can be easily extended to handle additional variables at both the individual and sib-pair levels and allows genetic and environmental influences and their interaction to be assessed directly in terms of the smoking phenotype, rather than than in a latent scale of smoking dependence, thus enhancing the interpretability of the regression coefficients.


Maarten W. Peeters1, Hermine H.M. Maes2, Martine A. Thomis1, Ruth Loos1,3, Albrecht L. Claessens1, Roeland Lysens1, Bart Vanden Eynde1, Robert Vlietinck3, and Gaston P. Beunen1
Evolution of genetic and environmental influences on regional fat distribution from early adolescence to young adulthood
1Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, Leuven Belgium 2Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond VA 3Center For Human Genetics, Katholieke Universiteit Leuven, Leuven Belgium
Address: Faculty of Physical Education and Physiotherapy, Tervuursevest 101, B-3001 Leuven, Belgium Phone: +32 16 32 90 86 Fax: +32 16 32 91 97 Email: Maarten.Peeters@flok.kuleuven.ac.be

An android pattern of regional fat distribution (RFD) has been shown to be associated with adverse health outcomes such as cardiovascular disease, diabetes and hypertension. The trunk-to-extremity skinfold ratio (TER), as an indicator of RFD, has been shown to be at least partly under genetic control. The aim of this study was to explore the evolution of genetic and/or environmental influences on TER variability from early adolescence (10yrs) into early adulthood (18yrs), by means of the simplex model (5 bi-annual observations). Subjects were male (n= 42) and female (n=42) twin pairs from the Leuven Longitudinal Twin Study. First a full simplex model, including common, specific, innovation and transmission parameters for additive genetic (A), common environmental (C) and unique environmental (E) factors, was fitted to the data to establish a baseline fit. Then a selected panel of reduced nested models was tested. The analysis favoured a model including innovation and transmission parameters for the A component, a time-specific E as well as a common E component and no C factors, for both males ([DELTA][chi]2:33.22, p:0.16) and females ([DELTA][chi]2:25.04, p:0.51). Gender differences in the relative contributions of the constituent components were observed. For the A component: at 14yrs, a peak value of 88.0% of the total variance was explained by A (males) versus 68.0% (lowest value) in females. At 18yrs the pattern was reversed: 59.4% and 86.9% for males and females respectively. As expected, the contribution of the innovation parameters, relative to the total A component, decreased reaching adulthood, the largest decrease occurring between 12yrs and 14yrs and between 16yrs and 18yrs for females and males respectively. This seems consistent with girls, on average, reaching maturity earlier than boys. The relative contribution of the common E factor to total E declined from 12yrs onwards for females and from 14yrs for males.


Alison Pike1 and Jenae M. Neiderhiser 2
Differential Parental Negativity: Objective Reality or in the Eye of the Beholder?3
1Psychology Group, School of Cognitive and Computing Sciences, University of Sussex, UK 2Center for Family Research, George Washington University, 2300Eye Street NW, Washington DC 20037 3Supported by the National Institute of Mental Health (MH-43373and MH-48825) and the William T. Grant Foundation
Address: Psychology Group, School of Cognitive and Computing Sciences, University of Sussex, UK Email: alisonp@cogs.susx.ac.uk

As part of the Nonshared Environment and Adolescent Development (NEAD) project, bivariate genetic analyses have been conducted for the associations between parental negativity and adolescent adjustment, using composites aggregated across parent reports, adolescent reports, and observations (A. Pike, S. McGuire, E. M. Hetherington, D. Reiss, and R. Plomin, 1996, Developmental Psychology 32, 590-603). The results indicated that parental negativity is significantly, but modestly, related to depressive symptoms and to antisocial behaviour via nonshared environmental processes independent of genetics. The relationships were, however, predominantly mediated by genetic factors. The purpose of the present study is to utilise the multiple informants within the NEAD study to explore the association between parental negativity and adolescent depressive symptoms both within and across different raters. Participants were 707 families with same-sex adolescent sibling pairs. The design included six sibling categories representing two family types: nondivorced and stepfamilies. The nondivorced families included 93 monozygotic (MZ) twin pairs, 98 dizygotic (DZ) twin pairs, and 95 full sibling pairs. Stepfamilies included 182 full sibling pairs, 109 half sibling pairs, and 130 unrelated sibling pairs. Each family member (mother, father, older and younger sibling) completed several questionnaires concerning parental negativity that were designed to tap how often and how intense disagreements were, as well as feelings of anger. Family members also assessed adolescent depressive symptomatology. Bivariate model-fitting was utilized in order to decompose these associations into their genetic and environmental constituents. In all six cases genetic factors significantly mediated the associations, however of most interest was the nonshared environmental mediation. The within-rater associations, as well as the within-parent correlation, were significantly mediated by nonshared environmental factors. The cross-generational associations were not significantly mediated by such factors. The most parsimonious explanation for these results is that the nonshared environmental mediation found is, infact, a result of systematic rater bias.


Michael F. Pogue-Geile1,2, Stephen Manuck1,2, Robert Ferrell3, and Thomas Debski1
Cognitive Function and Dopamine Transporter (DAT) Genetic Polymorphisms: A Twin and Genetic Association Study4
1Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA 2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA 3Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA 4Supported in part by NIH HL40962
Address: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA Phone: 412 624 8818 Fax: 412 624 5407 Email: mfpg@pitt.edu

Hypotheses about the brain correlates of many cognitive processes implicated in psychopathology predict a role for dopaminergic neurotransmission. The general aim of the present study was therefore to examine the extent to which different aspects of cognitive functioning may be associated with genetic variation in an important part of the dopaminergic pathway, the dopamine transporter (DAT). Polymorphisms in the DAT gene are especially interesting because of previous reports of associations with attention deficit disorder in children. To investigate this question, 410 young adult (18-30 years old) twins from the community were assessed with a neuropsychological test battery of twelve tests designed to tap major cognitive abilities and genotyped for one polymorphism in the DAT gene (a 40 bp core unit VNTR in the 3'-untranslated region). Analyses indicate a population association between these DAT gene alleles and measures of verbal short-term or working memory, which is consistent with prior studies of attention deficit disorder in children.


Tinca Polderman1, Toos van Beijsterveldt1,2, Caroline van Baal1, Therese Stroet1, Alexia Groot1, Jolande van der Valk1,2, Frank Verhulst2, Tom Achenbach3, Jim Hudziak3, and Dorret Boomsma1
Genetic analysis of DSM-oriented scales in 3 year-old Dutch twins as a function of parental Socio-economic status4
1Vrije Univ, Department Biological Psychology, Amsterdam 2Erasmus Univ, Sophia Kinderziekenhuis, Rotterdam 3Univ of Vermont, College of Medicine, Burlington, Vermont 4Supported by Sophia Foundation SSWO 165, NWO-904-57-94 and NIH-R01 MH58799
Address: VU, Dept of Biological Psychology, Van der Boechorststraat 1, 1081 BT Amsterdam The Netherlands Phone: +31 20 444 8789/8786 Fax: +3120 444 8832 Email: dorret@psy.vu.nl

CBCL data from young Dutch twins were used to obtain DSM-oriented scales assessing affective and anxious problems, pervasive developmental problems and oppositional and overactive behavior (Achenbach & Rescorla: Manual for the ASEBA Preschool Forms & Profiles. Burlington, VT: Univ Vermont, Dept Psychiatry, 2000). The large sample of 3-year-old twins (N = 6522 pairs) was subdivided into 3 groups, based on Socio-economic status (SES) of the parents (high, middle, low). Mean scores for all DSM-oriented scales are lower in the highest SES group and higher in the lowest SES group. For the twin correlations there is no clear pattern in the results as a function of parental SES.


Bernard P. Possidente, Jennifer Wishnow, Felicia Gomez, and Susan Kur
Genetic variation for circadian activity rhythm period among eight inbred mouse strains
Department of Biology, Skidmore College, Saratoga Springs, NY
Address: Biology Department, Skidmore College, Saratoga Spring, NY, 12866 USA Phone: 518 580 5082 Fax: 518 580 5071 Email: bposside@skidmore.edu

Inbred strain comparisons are a useful initial screen for genetic variation. Here we present initial estimates of additive genetic variance evident among eight inbred strains of mice (A/J, BALB/cJ, C3H/HeJ, C57BL/6J, DBA/2J, AKR/J, ILN/J and RIIIS/J) for free-running period of a circadian wheel-running activity rhythm. These inbred strains are similar to those used to create the base population of the HS outbred mouse strain (McClearn, G., Wilson, J., Meredith, W., 1970 in: Contributions to Behavior-Genetic Analysis: The Mouse as a Prototype, G. Lindzey and D. Thiessen, eds., Appleton-Century-Crofts, New York) which has been used successfully to accomplish artificial selection on a variety of Behavioral traits (e.g. Bult, A. and C.B. Lynch, 1997, Behav. Genet. 27, 231-240). Preliminary analysis shows a significant heritability for free-running circadian period in this population. These results predict a strong response to selection for circadian period, which would be useful for further experimental investigation of the genetic basis and functional properties of this central biological clock property.


Danielle Posthuma1, Dorret I. Boomsma1, G. Caroline C. van Baal1, and Eco J.C. de Geus1
Are faster brains also smarter?
1Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands
Address: D. Posthuma Vrije Universiteit Department of Biological Psychology Van der Boechorststraat 1 1081 BT Amsterdam The Netherlands Phone: +31 20 4448814 Fax: +31 20 4448832 Email: danielle@psy.vu.nl

The idea that rapid central nervous system processing may correspond to a smarter brain has been proposed in earlier studies and has recently been confirmed by studies reporting positive relations between inspection time and IQ (Posthuma, D., de Geus, E.J.C., and Boomsma, D.I., submitted,Behav. Genet. Luciano, M., Smith, G.A., Wright, M.J., Geffen, G.M., Geffen, L.B., and Martin, N.G., in press, Intelligence). An alternative way to index speed of central nervous system processing is through the assessment of brain oscillations via electroencephalographic (EEG) recording. The dominant frequency (peak frequency) with which an adult human brain oscillates is around 10 cycles per second, but large differences exist in individual peak frequencies. Earlier studies have related peak frequency positively to intelligence, arguing that a faster oscillating brain reflects rapid information processing associated with higher intelligence. This theory, however, still needs to be proven. In the present study data from 271 extended twin families (688 participants) were collected as part of a large ongoing project on the genetics of adult brain function and cognition. IQ was assessed with the Dutch version of the WAIS-IIIR. Individual peak frequencies were picked according to the method described by Klimesch (Klimesch, W, 1999, Brain. Res. Rev. 29,169-195). Results of structural equation modeling indicated that both peak frequency and IQ were moderately to highly heritable (47% and 89% resp.). The phenotypic correlation between alpha peak frequency and IQ, however, was 0.02. These results suggest that peak frequency can not be used as an intermediate phenotype for IQ and that genetic loci important for the speed with which the brain oscillates are not related to IQ.


Carol A. Prescott,1, Rebecca Cross2, John L. Horn,3, and Kenneth S. Kendler1
Sources of covariance between alcoholism and motivations for drinking
1Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, Richmond VA, USA 2Institute for Behavioral Genetics, University of Colorado, Boulder CO, USA 3Department of Psychology, University of Southern California, Los Angeles, CA, USA Supported by NIH Grants R01-MH/AA-49492, R01-AA/DA-09095 and K01-AA-00236. Thanks to Linda Corey and Lenn Murrelle, directors of the Mid-Atlantic Twin Registry and to Sarah Woltz, Frank Butera, Patsy Waring, Lisa Halberstadt, and Barbara Brooke who supervised data collection
Address: VIPBG, MCV/VCU, P.O. Box 980126, Richmond VA 23298-0126 Phone: 804 828 5968 Fax: 804 828 1471 Email: cprescott@hsc.vcu.edu

In a prior presentation (R. Cross, C. Prescott, J. Horn, & K. Kendler, Behavior Genetics Association, July 2000), we reported on the genetic and environmental sources of variation for four measures of drinking motivations from the Alcohol Use Inventory (AUI; Wanberg & Horn, 1983, American Psychologist 38, 1055-1069). We found that males and females had significantly different patterns of genetic and environmental contributions on all four scales. For the current paper we investigated the hypothesis that genetic liability for alcoholism is mediatedin part through genetic influences underlying drinking motivations. Lifetime diagnoses of alcohol abuse and dependence were available for >3000 pairs of adult twins sampled from the population-based Virginia Twin Registry, including >5000 drinkers who provided AUI data. The AUI scales accounted for 10-35% of the variation in risk for alcoholism in both sexes, with most of this being due to shared genetic variance. The strongest associations were obtained for the AUI scales which assess drinking to manage dysphoric mood and drinking to improve mental functioning. There was less evidence for genetic overlap between alcoholism and drinking in social situations or drinking to alleviate social anxiety.


Tom S. Price1, P.S. Dale2, T.C. Eley 1, and Robert Plomin1
Modularity and genetic correlation in cognitive development: A study of pre-school age twins
1 Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK 2 Department of Psychology, University of Columbia, Missouri
Address: Institute of Psychiatry, 111 Denmark Hill, London SE5 8AF, UK Phone: +44 20 7848 0961 Fax: +44 20 7848 0866 Email: t.price@iop.kcl.ac.uk

Multivariate genetic research suggests that from middle childhood onward correlations among cognitive abilities are largely due to shared genetic influences, implying a heritable general factor g. However, some research in infancy suggests that genetic influences may serve mainly to differentiate abilities. The current study investigates the overlap and stability of genetic influences on verbal and nonverbal cognitive abilities between infancy and childhood in a large representative sample of British twin pairs assessed using parental report instruments. A well-fitting multivariate genetic model shows up steady increases in the genetic overlap between verbal and nonverbal abilities from age 2 to age 3 and from age 3 to age 4, consistent with the developmental emergence of g.


Shaun Purcell1
Gene-by-environment interaction in twin and sib-pair analysis
1SGDP, Institute of Psychiatry, London, UK
Address: SGDP, 111 Denmark Hill, London, UK, SE5 8AF Phone: +44 20 7848 0931 Fax +44 20 7848 0866 Email: s.purcell@iop.kcl.ac.uk

The trait-mediating effects of specific environmental factors can be incorporated into twin and sib-pair analysis, modeled as simple covariates. In sib-pair quantitative trait loci (QTL) analysis, this may increase power to map QTL. Gene-by-environment interaction, on the other hand, represents a moderating effect of an environmental factor upon the expression of a genetic effect (or vice versa) and can also be incorporated into twin and sib-pair analysis. Instead of representing the additive genetic variance component, for example, as a single population average, eg. a2, this variance component is expressed as a function of an environmental moderator variable, M1, which might be different for each twin. The expected additive genetic variance component is then dependent on the moderator, i.e. (a + bAM1)2, assuming linear gene-by-environment interaction. That is, the genetic effect is partitioned into a mean part, a, and a moderator-linked part, bAM1. If the moderator has no effect, then bA = 0. The significance of the gene-by-environment interaction can be formally tested by fixing bA to 0 in a nested submodel and comparing model fit. In a completely analogous manner, gene-by-environment interaction can be incorporated in QTL linkage and association models. We explore the efficacy of such models and estimate the power to detect gene-by-environment interactions, with examples from real data.


Shaun Purcell, Pak Sham
Equivalence between Haseman-Elton and variance-components methods for sib-pair quantitative trait linkage analysis
Institute of Psychiatry, King`s College London, London, SE5 8AF
Address: SGDP Research Centre, Institute of Psychiatry, Decrespigny Park, Denmark Hill, London, SE5 8AF Phone: +44 20 7848 0931 Fax: +44 20 7848 0866 Email: s.purcell@iop.kcl.ac.uk

The Haseman-Elston regression method offers a simpler alternative to variance components models for the linkage analysis of quantitative traits. However, even the 'revisited' method, which uses the cross-product, rather than the squared-difference, in sib trait values, is in general less powerful than variance components models. Here, we clarify the relative efficiencies of existing Haseman-Elston methods, and show how a new Haseman-Elston method can be constructed to have the same power as variance components models. This method uses as the dependent variable a linear combination of squared-sums and squared-differences, where the weights are determined by the overall trait correlation between sibs in population. We show how this method can be used for the selection of maximally informative sib pairs for genotyping, and the subsequent analysis of such selected samples.


Chandra A. Reynolds1, Lars Feuk2, Margaret Gatz3,4, Ulf de Faire5, Anthony Brookes2, and Nancy L. Pedersen3,4
Association between APOE and ACE genotypes and cognitive decline6
1Department of Psychology, University of California Riverside 2Center for Genomic Research, Karolinska Institute 3Department of Psychology, University of Southern California 4Department of Medical Epidemiology, Karolinska Institute 5Institute for Environmental Medicine, Karolinska Institute 6Supported by NIH grants AG17561, AG0872, AG10175
Address: Department of Psychology, University of California Riverside, 1419 Life Sciences Psychology, Riverside, CA, 92521 Phone: 909 787 2430 Fax: 909 787 3985 Email: chandra.reynolds@ucr.edu

Polymorphisms in genes encoding apolipoprotein-E (APOE) and angiotensin-converting enzyme (ACE) were studied in relation to longitudinal cognitive performance among older adults. APOE is the major genetic risk factor for Alzheimer's disease (AD), while ACE has been associated with cardiovascular disease outcomes as well as cognitive impairment and AD. The influence of the APOE e-4 allele and the Aluinsertion/deletion polymorphism of the ACE gene on cognitive decline was investigated in a longitudinal sample of individuals aged 50 years and older from the Swedish Adoption /Twin Study of Aging (SATSA) and Study of Dementia in Swedish Twins. Longitudinal cognitive data encompassed verbal, spatial, memory and perceptual speed domains. APOE genotyping was available for 637 twins with cognitive data. The APOE e-4 allele was associated with a positive dementia status and among non-demented twins accelerated cognitive change over time on Symbol Digit--a perceptual speed task. ACE was genotyped for 557 twins with cognitive data. The ACE polymorphism was not significantly associated with dementia status. The absence of the I allele was associated with greater overall decline across cognitive domains but was not significantly related to rate of change on specific cognitive tasks. The association of APOE e-4 with decline on perceptual speed has previously been reported in one study of community dwelling elderly. The relationship of ACE with overall cognitive decline is consistent with previous studies suggesting the D allele is related to cognitive impairment.


Sally-Ann Rhea1, and Robin P. Corley1
Family history influences on adopted adolescents' substance experimentation.2
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309-0447 2Supported by grants HD10333, MH43899 and DA11015
Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309-0447 Phone: 303 492 2822 Fax: 303 492 8063 Email: rhea@colorado.edu

Previous findings from the Colorado Adoption Project (CAP) support the pattern found by other researchers for small but significant differences between adoptees and non-adoptees in measures of adolescent adjustment, including likelihood of substance experimentation (Corley, R.P. & Rhea, S.A., 1999, Behav. Gent. 29, 352). For the CAP sample, acceptance of adoption and TPQ novelty seeking were the most consistent predictors of increased substance experimentation for the adolescent adoptees. In contrast, a questionnaire report of biological parent substance use administered at entry to the project was an inconsistent predictor. We have now examined an indicator of antisocial personality from both biological and adopting parents for 93 adopted adolescents for whom these parental data are available. Using this measure comprised of several items from the entry questionnaire, we find mean differences for the biological mothers between offspring experimenters and abstainers, with a t-value of 2.25, p<.05, but no differences for adopting mothers or fathers. Because the questionnaire data are not complete for biological parents and due to those parents' relatively young age, we also review additional measures of substance use and mental health problems in both the biological parents and their relatives as found in family history interviews from adoption agency records.


Soo Hyun Rhee1, John K. Hewitt1, Susan E. Young1, Robin P. Corley1, Thomas J. Crowley2, and Michael C. Stallings1
The etiology of comorbidity between substance dependence and conduct disorder in adolescents 3
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 2Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262 3Supported by NIDA grants DA-05131 and DA-11015
Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309 Phone: 303 492-4631 Fax: 303 492-8063 Email: Soo.Rhee@colorado.edu

The conclusions of past studies examining the comorbidity among substance use disorders and the comorbidity between substance use disorders and conduct disorder are conflicting. Here, we address the question of the causes of comorbidity among substance dependence diagnoses and the comorbidity between substance dependence and conduct disorder in adolescents with antisocial substance abuse. DSM-III-R substance dependence diagnoses and conduct disorder diagnoses were assessed in a combined sample of a clinical sample of adolescents in treatment for antisocial substance abuse (216 probands and their closest-age siblings) and a control sample (210 controls matched to the probands and their closest-age siblings). A model fitting approach was used to test 12 alternative hypotheses for the causes of comorbidity. The best supported hypotheses for the comorbidity among substance dependence diagnoses and the comorbidity between substance dependence and conduct disorder were a model hypothesizing the comorbid disorders as alternate forms of a single underlying liability distribution and models hypothesizing two very highly correlated liability distributions for the comorbid disorders.


Frances J Rice1 2, Gordon T Harold2, and Anita Thapar1
Extreme Depressive Symptoms in Children and Adolescents
1 Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom 2 School of Psychology, Cardiff University, Cardiff, United Kingdom
Address: Department of Psychological Medicine, 4th Floor University of Wales College of Medicine, Cardiff, CF4 4XN, United Kingdom Phone: 029 20 742201 Fax: 029 20 747839 Email: Ricef@cardiff.ac.uk

Previous studies have used DF analysis (J.C. DeFries & D. W. Fulker, 1985, Behav. Genet. 15, 467-473) to compare the aetiology of normal and abnormal levels of depressive symptoms in children and adolescents (R Rende et al 1993 JCPP 34, 1387-1398; H Gjone et al. 1996, Behav. Genet. 26, 419-426; K Deater-Deckard et al 1997; JCPP 38, 515- 525; T.C. Eley 1997 JCPP 38, 861-865). However, they have reported conflicting findings. The present study used a large population-based sample of twins (N 1500 pairs) aged 9-18 years to compare the heritability of extreme self and parent rated depressive symptoms and symptoms within the normal range. For parent rated data, genetic factors were less important for extreme group membership than scores within the normal range. Further results will be presented.


Marjolein J. H. Rietveld1, Toos van Beijsterveldt1, Jolande C. van der Valk2, F. C. Verhulst2, and Dorret I. Boomsma1
A Longitudinal Study of Common Childhood Psychopathology3
1Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands 2Department of Child and Adolescent Psychiatry, Sophia Children's Hospital, Rotterdam, The Netherlands 3Supported by USF (grant number 96/22)
Address: Department of Biological Psychology, Vrije Universiteit, room 1F 57, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands Phone: +31 20 4448812 Fax: +31 20 4448832 Email: mjh.rietveld@psy.vu.nl

At three occasions, we collected data on behavior and emotional problems in a large sample of Dutch twins, born between 1986 and 1991. Twins were aged 3, 7 and 10 years. Nearly 3700 parents completed the Child Behavior Checklist (CBCL) on at least one of these occasions. Around 2000 pairs have complete longitudinal data by maternal report. Of these cases, nearly 50% of the fathers completed an additional CBCL. Compared to fathers, mothers report more behavior problems in their children. The discrepancy between parents is observed for each syndrome, for both genders, and at each age. When boys are compared to girls, we find most significant differences for syndromes that are related to externalizing problem behavior. At age 3, boys already display more overactive, aggressive, and oppositional behavior. Twin correlations calculated for each trait at each age are suggestive of an ADE model for overactive/attention problems and an ACE model for the other syndromes. Concerning stability in problem behavior, phenotypic correlations are moderate for the interval from age 3 to age 7 (between .20 and .50), and large for the interval from age 7 to age 10 (between .40 and .75). Externalizing problem behaviors display more stability compared to internalizing problem behaviors. The observed stability in problem behavior appears to be due to genetic influences. We intend to explore the data by using a multi-informant longitudinal design to address the genetic and environmental contributions to stability and change in common psychopathology across childhood age.


Marjolein J. H. Rietveld1, G. Caroline M. van Baal1, Meike Bartels1, and Dorret I. Boomsma1
Continuous and Discontinuous Cognitive Development2
1Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands 2Supported by USF (grant number 96/22)
Address: Department of Biological Psychology, Vrije Universiteit, room 1F 57, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands Phone: +31 20 4448812 Fax: +31 20 4448832 Email: mjh.rietveld@psy.vu.nl

In addition to continuous growth, cognitive abilities during childhood show clear discontinuous developmental patterns. An example of discontinuous cognitive development is the Piagetian conservation ability, which generally emerges in children around age 7 years. As part of a longitudinal twin study we collected data on both continuous and discontinuous cognitive development at four occasions during childhood. Continuous developmental data were collected by means of an intelligence test, administered to 209 twin pairs at ages 5, 7, 10 and 12 years. Discontinuous data were collected by means of a computerized version of Piaget's conservation ability task, administered to the same twins at age 7. Children were classified as conservers (54%) or non-conservers (46%). At each age, conservers achieved an intelligence score which was significant higher compared to the intelligence score achieved by non-conservers. This remained significant after correction for variation in age within each occasion of measurement. The significant effect appeared due to a large effect for nonverbal or performal cognitive ability. A trend was observed for verbal cognitive ability. Heritability is established for both conservation ability and intellectual development. We attempt to explore the underlying sources of the observed association between these two measures of cognitive development by using genetic structural modeling.


Früaut;hling Rijsdijk, and Pak Sham
An index of multipoint polymorphism information content (MPIC)
Institute of Psychiatry, King`s College London, London, SE5 8AF
Address: SGDP Research Centre, Institute of Psychiatry, Decrespigny Park, Denmark Hill, London, SE5 8AF Phone: +44 20 7848 0890 Fax: +44 20 7848 0866 Email: spjgfvr@iop.kcl.ac.uk

We have previously shown that the non-centrality parameter (NCP) for sib pair quantitative trait linkage analyses under a variance components model is proportional to the variance of the estimated proportion of IBD sharing (pi-hat) between sibs (F.V. Rijsdijk et al., 2001, Eur. J.Hum. Genet., in press). The variance is 0 in the absence of IBD information, and 1/8 in the case of complete IBD information. In this paper we show that the variance of pi-hat is in fact proportional to the polymorphism information content (PIC), for sib pairs with known genotypes on themselves and both parents. We further extend a multipoint IBD estimation method (D.W. Fulker et al., 1995Am.J.Hum.Genet. 56, 1224-1233) to derive the variance of pi-hat estimated from multiple markers. This is proposed as a index of multipoint polymorphism information content, since it is analogous to the PIC, and it is proportional to the NCP for linkage.


Richard J. Rose1, Richard J. Viken1, Danielle M. Dick1, Lea Pulkkinen2, and Jaakko Kaprio3
Shared Environmental Effects on Behavior: Distinguishing Familial from Non-Familial Sources with Data from Twins and their Classmate Controls4
1Department of Psychology, Indiana University, Bloomington, IN 47405 2Department of Psychology, University of Jyv„skyl„, Finland 3Department of Public Health, University of Helsinki, Finland 4FT12 is supported by NIAAA (AA-09203) and the Academy of Finland
Address: Department of Psychology, Indiana University, Bloomington, Indiana 47405 Phone: 812 855 8770 Fax: 812 855 4691 Email: rose@indiana.edu

In typical twin study data, common environment is estimated from all non-genetic effects that make twin sibs alike: familial effects of parenting style and household atmosphere, as well as influences from neighborhoods, schools, and common peers. To distinguish these two sources of effects, one approach is to add classmate controls to a representative and geographically diverse sample of twin children. We have obtained such data in FinnTwin12, a population-based twin sample, with a randomly-selected, gender-matched classmate control for each twin; twins and their controls were assessed at age 11- 12, in classrooms throughout Finland. Measures included teacher ratings on the full sample of same-sex twin and control dyads (N~5,600 individual twins and their controls) and a self-report questionnaire and peer nominations for a sub-sample (N~2,800 twins and controls). The control dyads share neither genes nor household environments, but controls are matched to twins on birth cohort and gender, live in the same municipality, and attend the same school. The twin-control and control-control dyads exhibit some significant Behavioral similarities (e.g., for substance use and misconduct), but not for household- specific measures (e.g., saying bedtime prayers in early childhood). Formal modeling of data from the double-dyads formed by twins and classmate controls yields some substantial estimates of extra- familial environmental effects, extending earlier analyses of twins and their classmates (e.g., in the Add Health study) and inviting further research into the role of such influences in Behavioral development.


Pierre L. Roubertoux1,2, Isabelle Le Roy1, Danièle Migliore-Samour 1, and Améziane Cherfouh1
Analysis of quantitative trait loci for Behavioral laterality in mice
1FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 45071 Orléans cedex 2, France 2University of Orléans
Address: FRE 2134 CNRS, Génétique, Neurogénétique Comportement, 3B rue de la Ferollerie, 45071 Orléans cedex 2, France Phone: 33 238 257970 Fax: 33 238 257979 Email: rouber@cnrs-orleans.fr

Left handedness which has a prevalence of 7% in western populations1 is associated with immune2-4 and mood2,5-7 disorders. As prevalence reaches 21% in offspring of probands1 supporting a genetic contribution, gene identification should elucidate the physiopathological pathways underlying both laterality and mechanisms of these associations. A high conservation of brain and Behavioral asymmetries across species7 justifies using mice for identifying genes linked to laterality. Direction of laterality (preferential use of either left or right paw) and degree of laterality (absolute difference between the use of right and left paw) were measured independently with forepaw and hind paw in F2s derived from C57BL/6by (B6) and NZB (N) mice. QTLs emerged for degree only. One for forepaw (LOD score = 5.6) and another for hind paw (LOD score = 7.2) were both located on chromosome 4. Their chromosomal distance was smaller than their respective confidence intervals suggesting a one-QTL model. The map position of Lepr gene (leptin receptor) within this chromosomal segment supports the hypothesis of an implication of gonadal steroids in degree of laterality.


David C. Rowe1, and Kristen C. Jacobson2
A Twin and Sibling Study of Cigarette Smoking in the National Longitudinal Study of Adolescent Health
1Department of Family Studies and Human Development, Campus Box 210033, University of Arizona, Tucson, AZ 85721 2VIPBG, MCV/VCU, PO Box 980126, Richmond, VA 23298-0126
Address: Department of Family Studies and Human Development, Campus Box 210033, University of Arizona, Tucson, AZ 85721 Phone: 520 621 7127 Fax: 520 621 3401 Email: dcr091@ag.arizona.edu

Twins and siblings in the National Longitudinal Study of Adolescent Health's wave 2 (1995) were surveyed about their level of cigarette smoking during the past month. The pattern of same-sex sibling correlations on smoking suggested genetic influence: identical twins, r=.65, N=195; fraternal twins, r=.47, N=145; full siblings, r=.37, N=472; half-siblings, r=.12, N=100. Regression analyses indicated that full siblings who spent more time together were more alike in their smoking behavior. In other sibling groups, time together did not moderate siblings' resemblance. Additive genes (A), shared environment (C), and non-shared environment (E) were represented as latent variables and evaluated on the siblings' raw data using the structural equation modeling program Mx. An ACE model without moderation provided a baseline fit (-2log likelihood = 3,771.9). Two models, AE+time and ACE+time, were tried with time together added as a continuous moderator of the shared environmental effect. Both models fit better than the base ACE model, with the ACE+time model being superior (change in chi square = 14.0). The variance components estimates were h2= .52, c2= .13, and e2= .35. The time together effect added an extra-dose of variance/covariance in the full sibling group only (variance component = .13). As modeled, this time together effect applies mathematically to the additive genetic variable as well; indeed, with moderation in only one of four groups, moderated A cannot be distinguished from moderated C. Thus, this effect could be either a gene by C interaction, whereby additional genetic influences on smoking would be expressed in a similar manner only when full siblings share similar peer groups, or a direct environmental effect, whereby full siblings who spend more time together would be similarly exposed to environmental influences on smoking (e.g., peer influences).


Stephanie Schmitz1
Attention Problems and Emotionality at Ages 7 and 12
1Institute for Behavioral Genetics, University of Colorado, CO 80309 2Supported by NIH grants MH-43099 and HD-10333. S.S. is supported by grant MH-62116
Address: Institute for Behavioral Genetics, Campus Box 447, University of Colorado, CO 80309; Phone: 303 492 0835 Fax: 303 492 8063 Email: schmitzs@colorado.edu

The current study looked at the relationship between attention problems and personality. Data were collected in a twin and an adoption sample at the ages of 7 and 12 with the Teacher Report Form (TRF; Achenbach, 1991, University of Vermont) and the teacher-rated Colorado Childhood Temperament Inventory (CCTI; Rowe & Plomin, 1977, Journal of Personality Assessment 41, 150-156). Sample sizes ranged between 911 and 1035 at age 7 and 583 and 606 at age 12; the number of complete pairs ranged from 51 (unrelated siblings) to 120 (MZs) at age 7 and from 29 (unrelated siblings) to 60 (MZs) age 12. The stability of behavior ratings was medium (r=.45) while that for temperament was low (r=.23) over the five-year span. The Emotionality scale of the CCTI correlated with all aspects of the TRF-Attention Problems scale (overall attention problems, hyperactivity/impulsivity, and inattention) at around .30 at age 7 and .45 at age 12. These correlations were mainly genetically mediated, more so at age 7 than at age 12. The correlations between Attention Problems at age 7 and Emotionality at age 12 (r=.30) were about twice as large as those between Emotionality at age 7 and Attention Problems at age 12 (r=.17). This suggests that Attention Problems may lead to emotional problems, rather than the Emotionality aspect of personality leading to Attention Problems.


Nancy L. Segal1, Sara Arad1
Social Closeness and Familiarity in MZA and DZA Twin Pairs2
1Psychology Department, California State University, Fullerton, California 92834 2Supported by a faculty research award from California State University, Fullerton
Address: Psychology Department, California State University, Fullerton, California 92834; Phone: 714 278 2142 Fax:714 278 4843 Email: nsegal@fullerton.edu

Perceptions of social closeness and familiarity between reared apart monozygotic (MZA) and dizygotic (DZA) twins were assessed via a Twin Relationship Survey. This study is the first to systematically examine social relatedness in this unique twin sample. Participants included 44 MZA and 33 DZA twin pairs plus several individual twins and triplets from the Minnesota Study of Twins Reared Apart. A repeated measures anova showed significantly greater closeness and familiarity among MZA than DZA twin pairs. As expected, MZA intraclass correlations significantly exceeded DZA correlations for current closeness and current familiarity. It was also found that twins' current closeness and familiarity scores for their newly found co-twins exceeded those for the unrelated siblings with whom they were raised. Other analyses showed that correlations between twins' perceptions of their current physical resemblance and current social closeness and familiarity were positive and statistically significant. In contrast, most correlations between social relatedness ratings and contact time measures were non-significant. Finally, exploratory study of associations between twins' social relatedness and similarities in personality traits, interests, values and educational background were conducted. The findings support various theoretical perspectives anticipating greater cooperation and affiliation among close relatives, compared to distant relatives and non-relatives.


Atsushi Senju1, Juko Ando2, Yutaka Ono3, Toshikazu Hasegawa1, and Mariko Hiraiwa-Hasegawa4
Genetic and environmental influences on 'theory-of-mind' in Japanese adult twins
1Graduate School of Arts and Sciences, The University of Tokyo, Japan 2Faculty of Letters, Keio University, Japan 3School of Medicine, Keio University, Japan 4School of Political Science & Economics, Waseda University, Japan
Address: Hasegawa Lab., Department of Cognitive and Behavioral Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan

'Theory-of-mind', the ability to understand the mental states of others, is thought to play an important role in human social interaction and communication. In a recent twin study, a strong genetic influence on theory-of-mind ability among 3-year-old children was reported (C. Hughes, and A. L. Cutting, 1999, Psychol. Sci. 10, 429-432). However, the extent of both genetic and environmental influences on the subsequent development of theory-of-mind remains unknown. In this study we examined individual differences in theory-of-mind ability in a population of adult twins. 85 pairs of Japanese twins (17-26 years old) participating in the Keio Twin Project were tested on a Japanese language version of the 'Eyes Test' (S. Baron-Cohen, T. Jolliffe, C. Mortimore, and M. Robertson, 1997, J. Child Psychol. Psychiat 38, 813-822), an advanced test of theory-of-mind. In this task, participants are presented with photographs of the eyes of others and asked to assess the mental states of their owners. A CE model best-fitted the results, suggesting a moderate influence of shared environment and a strong influence of non-shared environment. Results indicated that there was no genetic influence on individual differences in theory-of-mind, at least among normally developed adults. Implications for evolutionary psychology will be discussed.


Michael S. Siniatchkin1, 2, and Wolf-Dieter Gerber2
Genetics of the contingent negative variation in migraine3
1Department of Child and Adolesceent Psychiatry, University of Goettingen, D-37075 Goettingen, Germany 2Department of Medical Psychology, University of Kiel, D-24105 Kiel, Germany 3Supported by the German Research Foundation Grant Ge500/4-1, 4-2
Address: Department of Child and Adolescent Psychiatry, University of Goettingen, Von-Siebold-Str. 5, D-37075 Goettingen, Germany, Phone: +49 551 39 64 38 Email: msiniat@gwdg.de

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate genetics of migraine is the evaluation of biological elementary endophenotypes in migraineurs and individuals at risk. Migraine patients are characterised by increased amplitude and reduced habituation of the early component of the contingent negative variation (CNV)(W.D. Gerber and J. Schoenen, 1998, Cephalalgia 18, Suppl 21, 11). In this study the CNV (reaction time paradigm, Cz with linked mastoids, 0,03 35 Hz filters, impedance less than 5 kOhm, EOG control) was recorded in 50 migraineurs, 35 healthy high-risk subjects with a positive family history of migraine (FHP) and 35 healthy low-risk individuals without a positive family history (FHN) as well as 50 families (196 subjects), each with a child and parent suffering from migraine, and 41 healthy families (131 subjects) without migraine. FHP participants demonstrated the same early CNV abnormalities and distribution among early CNV characteristics than migraineurs. The amplitude of the early CNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives (r = 0.57, p < 0.001). The higher the density of affected individuals in the family, the more pronounced were CNV abnormalities in relatives. In families the correlation analysis demonstrated significant correlation between parents suffering from migraine and their migraine children (for the CNV amplitude: r = 0.69, CNV habituation: r = 0.48; p < .001) and between healthy parents with migraine relatives and their migraine children (for the CNV amplitude: r = 0.73, CNV habituation: r = 0.51 p < .001). Mathematical analysis of curve morphology (Monte-Carlo) confirmed these results. The study provides evidence that familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the early CNV, and that the early CNV component may be used as a functional-genetic vulnerability marker in further research of migraine genetics.


Wendy S. Slutske1, Andrew C. Heath 2, Kathleen K. Bucholz2, Pamela A. F. Madden2, Dixie Statham3, & Nicholas G. Martin 3
Examining sex and cohort differences in the etiology of conduct disorder: A study of 6,342 adult twin pairs 4
1 Missouri Alcoholism Research Center, Department of Psychological Sciences, University of Missouri, Columbia, MO 2Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St Louis, MO 3Queensland Institute of Medical Research, Brisbane, Queensland, Australia 4Supported by National Institutes of Health grants AA00264, AA07728, AA09022, AA10249, DA00272, DA12854, and AA11998, and by the Australian National Health and Medical Research Council.
Address: Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211 Phone: 573 882 4043 Fax: 573 882 7710 Email: SlutskeW@missouri.edu

Behavioral genetic studies of antisocial behavior still tend to produce far-ranging estimates of heritability, suggesting that there may be important moderators of genetic risk factors. Within-study examination of potential moderating variables may be useful in reconciling the cross-study differences. In this study, we examined the possible moderating influence of sex and birth year on estimates of genetic influences for DSM-III-R conduct disorder (CD), retrospectively reported. Structured psychiatric telephone interviews were conducted with 12,105 individuals from 6,342 pairs from the Australian Twin Registry; about half of the participants (born 1902-1964) were interviewed in 1992-1993 and the other half (born 1964-1971) were interviewed in 1996-2000. The lifetime prevalences of CD were much higher among the later-born participants (7% among women, 27% among men) than among the earlier-born (3% among women, 18% among men), and this was still true among a subsample of 5,270 participants who were the same age at interview (30-35 years), but were born in different years (1956-1963 versus 1964-1970), which rules out retrospective bias as an explanation for the cohort differences in the lifetime prevalences of CD. Despite the large sex and cohort differences in the prevalences of CD, we failed to detect in preliminary analyses, even in this large sample, a significant moderating influence of sex or birth year cohort on the contribution of genetic factors to CD risk. The heritability estimates (from full models) were 52% (95% CI = 30-69) in the combined sample, 61% (95% CI = 25-78) in the earlier-born cohort, 46% in the later-born cohort (95% CI = 18-68), 37% (95% CI = 0-79) among women, and 58% (95% CI = 12-70) among men. The results of additional analyses using more sensitive tests of moderation will be presented; nonetheless, the results of the preliminary analyses support the conclusion that CD is a disorder of moderate heritability, and that the genetic contribution to risk for CD is not dependent upon sex or the changing environmental contexts that are associated with being raised in different eras.


Erica L. Spotts 1 and David Reiss 1
Genetic and environmental mechanisms underlying the association between marriage and depressive symptoms 2
1The Center for Family Research, The George Washington University, Washington, DC 2The Twin Moms project is supported by grant RO1MH54610 from the National Institutes of Mental Health
Address: Center for Family Research, The George Washington University, 2300 I St. NW Room 613, Washington, DC 20037 Phone 202 994 2404 Fax: 202 994 4812 Email: elspotts@gwu.edu

Depressive symptoms are much more common in women than in men (R. C. Kessler, K. A. McGonagle, S. Zhao, C. B. Nelson, M. Hughes, S. Eshlemen, H. U.Wittchen & K. S. Kendler, 1994, Archives of General Psychiatry 51, 8-19). Many explanations have been offered in an attempt to explain this discrepancy. Not the least of these is the role of interpersonal relationships in the development and maintenance of depressive symptoms. Marital relationships are most often linked to depression (S. R. Beach, F. D. Fincham & J. Katz, 1998, Clinical Psychology Review 18 , 635-661). While depression has been found to be approximately equally influenced by both genetic and nonshared environmental factors (K. S. Kendler, M. C. Neale, R. C. Kessler, A. C. Heath & L. J. Eaves, 1993, Archives of General Psychiatry 50 , 589-596), marital quality is predominantly influenced by nonshared environmental factors with small amounts of genetic influence (E. L. Spotts, J. M. Neiderhiser, H. Towers, K. Hansson, P. Lichtenstein, M. Cederblad, N. L. Pedersen, O. Elthammer, & D. Reiss, Submitted, Genetic and environmental influences on marital relationships). Therefore, these analyses will focus on identifying sources of nonshared environmental influences for the associations between marital relationships and depression in women. Depressive symptoms and three important aspects of the marital relationship-- social support, expressed emotion, and marital quality--were assessed in a Swedish sample of 326 adult twin women and their families. Preliminary bivariate analyses indicate that the underlying mechanisms for these associations are mildly genetic and predominantly nonshared environmental in nature. Additional analyses will include social support, expressed emotion, and marital quality in the model to assess the extent to which each of these characteristics of marriage predict depression independently of the others.


Michael C. Stallings1, John K. Hewitt1, Jeff M. Lessem1, Susan E. Young1, Robin P. Corley1, Susan K. Mikulich2, and Thomas J. Crowley2
Modeling the familial transmission of alcohol dependence symptom counts in clinical and control family pedigrees3
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309 2Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262 3Supported in part by NIH Grants DA-05131 and DA-11015
Address: Institute for Behavioral Genetics Campus Box 447 University of Colorado Boulder, CO 80309-0447 Phone: 303 492 2826 Fax: 303 492 8063 Email: Michael.Stallings@Colorado.Edu

The use of quantitative measures of alcoholism risk in family analyses can provide increased power over qualitative diagnoses. However, substance dependence symptom counts (e.g., DSM criteria) are not continuously or normally distributed and require alternative analytic methods to those commonly applied to continuous measures. We show, through the use of both simulated data and obtained family data, the advantages of treating symptom counts as ordered categorical data in multiple-threshold family transmission analyses. Data come from 200 families ascertained through male adolescent probands in treatment for substance abuse and conduct disorder and 200 control families with an adolescent matched to characteristics of the treatment probands. Symptoms counts are based on DSM-III-R criteria for alcohol dependence obtained through structured dia gnostic interview (CIDI-SAM). Results suggest substantial vertical parent-offspring transmission of risk for alcohol dependence and demonstrate the increased power of joint family analyses incorporating data from both selected and control families.


Anita Thapar1, Jane Holmes1, Anthony Payton2, Jenny Barrett2, Richard Harrington2, Peter McGuffin4, Michael Owen1, William Ollier2, Michael Gill3, Aiveen Kirley3, Ziarih Hawi3, Michael Fitzgerald3, Philip Asherson4, Sarah Curran4, John Mill4, Alison Gould4, Eric Taylor4, Lyndsey Kent5, Nick Craddock5, and Jane Worthington1
Evidence of Association between DRD4 and ADHD with conduct disturbance6
1Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, Wales 2ARC Epidemiology Unit and Department of Child and Adolescent Psychiatry, University of Manchester, Manchester, England 3Departments of Psychiatry and Genetics, Trinity College, Dublin, Ireland 4Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, England 5Department of Psychiatry, University of Birmingham, Birmingham, England 6Supported by Wellcome Trust, Medical Research Council (UK), Action Research
Address: Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff. CF14 4XN, Wales, UK Phone: +44 29 2074 3241 Fax: +44 29 2074 7839 Email: thapar@cardiff.ac.uk

Recent family (S.V. Faraone, J. Biederman, and M.C. Monuteaux, 2000, Genet. Epidemiol. 18, 1-16) and twin study findings (A. Thapar, R. Harrington, and P. McGuffin, 2001, Br. J. Psychiatry in press, Examining the comorbidity of ADHD related behaviours and conduct problems using a twin study design) suggest that Attention Deficit Hyperactivity Disorder with comorbid conduct problems may represent a subtype of ADHD with greater genetic loading Although there have now been independently replicated findings of a positive association with the DRD4 7 repeat allele and ADHD, some groups have failed to show these findings. Previous TDT analysis of UK and Eire samples had been negative. It is not clear what accounts for the differences in these findings from different studies. We set out to further examine the DRD4 polymorphism in a sub-sample of children with ADHD and comorbid conduct disturbance. The sample comprised 67 children recruited from a larger cohort of children with ADHD from Greater Manchester, Ireland, London and Birmingham Clinics. TDT analysis, which had previously yielded negative results for the total sample, showed evidence of association between the DRD4 7 repeat allele and "ADHD with conduct problems" (24 transmissions, 13 non transmissions, p=0.05). These results provide further support for the role of DRD4 in ADHD. Although these results require replication in other samples, they suggest that ADHD when comorbid with conduct problems may represent a more genetic subtype at a molecular level.


Martine A.I. Thomis1, Hermine H.H. Maes2, Maarten Peeters1, Ruth Loos1,3, Roeland Lysens 1, Albrecht L. Claessens1, Bavo Vanden Eynde1, Robert Vlietinck3, and Gaston Beunen1
Genetic control of skeletal maturation during growth
1Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, B-3001 Leuven, Belgium 2Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0003 3Center for Human Genetics, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
Address: Faculty of Physical Education and Physiotherapy, Tervuursevest 101, B-3001, Leuven, Belgium Phone: +32 16 329086 Fax: +32 16 329197 E-mail: Martine.Thomis@flok.kuleuven.ac.be

Somatic and motor performance characteristics have been studied in children and adolescents in cross-sectional or longitudinal designs to develop growth curves of these characteristics. Twin studies on younger age cohorts are mostly studied based on chronological age. However, variability in maturation is substantial and individual differences in tempo and timing correlate with both somatic and performance characteristics. In the Leuven Longitudinal Twin Study, yearly radiographs of the left wrist were taken (10-18 years of age) in 105 twin pairs, to estimate skeletal maturity scores based on the Tanner-Whitehouse II method (Tanner et al., 1983, Assessment of skeletal maturity and prediction of adult height (TW2 method). London: Academic Press. Weighted Radius-Ulna-Short bones (RUS), Carpus bones (CARP) and all 20 bones (TWII-20) scores as well as summed bone scores (RUS-s, CARP-s, TWII-s, Proximal epiphyses P-s, Distal epiphyses D-s, Central bones C-s) were determined at all ages. At ten years-of-age, considered as a pre-pubertal assessment in boys and girls, variation in maturity scores is largely explained by additive genetic factors (88-96% for RUS, CARP, TWII-20) with evidence for gender heterogeneity and influences of common environmental factors (c2=34-43% for RUS-s, Carp-s, D-s). At 13 yrs, similar heritability estimates are found for the weighted scores, for the summed bone scores, gender heterogeneity is present with larger cý estimates in girls than in boys (females: h2:0.04-0.66, c2:0.18-0.81, e2:0.15-0.24; males: h2:0.38-0.66, c2:0.18-0.42, e2:0.17-0.28). Since maturity scores, by definition, reach a definite endpoint (complete fusion of diaphyses and epiphyses), 'individual' growth curves can be determined for all twins, with differentiation in timing to reach this end point. Latent growth curve fitting will be applied to study the genetic and environmental contributions to the underlying growth curve parameters, as well as the estimation of time-specific contributions of genes and environmental factors.


Eric Turkheimer1, Andreana Haley1, Brian D'Onofrio1, Mary Waldron1, Robert E. Emery1, and Irving I. Gottesman1
Socioeconomic status modifies heritability of intelligence in impoverished children
1Department of Psychology, University of Virginia, Charlottesville, VA
Address: Department of Psychology, P.O. Box 400400, University of Virginia, Charlottesville, VA 22904-4400 Phone: 804 982 4732 Fax: 804 982 4766 Email: turkheimer@virginia.edu

It has long been suspected on theoretical grounds that the relation between shared environment and intellectual ability in childhood might be characterized by a nonlinear function or a threshold, whereby differences among middle class environments are not strongly related to IQ, but exposure to highly deprived environments has a substantial effect. Empirical evidence for this hypothesis has been difficult to come by for two reasons: Few twin samples include twins raised in serious poverty, and until recently there have been severe restrictions on our ability to fit biometric models including continuous interactions with external variables. We report an analysis of 350 MZ and DZ twin pairs collected from the National Collaborative Perinatal Project (NCPP) which included perinatal data on 53,000 children born to 40,000 mothers. The children were tested with the Stanford Binet at age four and the WISC at age 7. A high proportion of the children were raised in severely impoverished circumstances. We use novel scatterplot smoothing methods as well as Mx-based moderator models to demonstrate a substantial interaction between ACE models of WISC IQ and socioeconomic status. In the poorest families, practically all of the variability is accounted for by shared environment, and none by genotype; in the best off families, the situation is the exact reverse. The effect appears to be strongest for intellectual measures related to crystallized IQ.


G. Caroline M. van Baal1, Dorret I. Boomsma1, and Eco J.C. de Geus1
Genetics of electroencephalographic coherence and intelligence in young twins2
1Vrije Univ, Department Biological Psychology, Amsterdam 2Supported by NWO-575-65-052 and Van Coeverden Adriani Stichting
Address: VU, Dept of Biological Psychology, Van der Boechorststraat 1, 1081 BT Amsterdam The Netherlands Phone: +31 20 444 8802/8787 Fax: +31 20 444 8832 Email: gcm.van.baal@psy.vu.nl

The search for genes influencing cognitive abilities can be aided by the use of intermediate phenotypes. Essential requirements for such research is that both phenotypes as well as the association between them show high heritabilities. An important advantage of using an intermediate phenotype is that it may guide in finding the psychophysiological mechanisms underlying cognition. Unfortunately, research in this area has not yet shown substantial successes, with possible exceptions of speed of information parameters such as inspection time, reaction times and P300 event related potentials. In the current study we focus on another possible mechanism, namely neuronal connectivity of the brain, as indexed by coherence in the electroencephalogram (EEG). EEG coherence is a measure of cross-correlation between EEG recordings at different sites on the scalp. It expresses a developmental pattern that closely relates to changes in cognitive abilities in young children. To study the association between cognition and coherence, EEG and IQ data were collected twice for 209 five-to-seven-year-old twin pairs. Both phenotypes show substantial heritabilities (D.I. Boomsma and G.C.M. van Baal, 1998, Devel.Neuropsych. 14, 115-126; G.C.M. van Baal, E.J.C. de Geus, D.I. Boomsma, 1998, Behav. Genet. 28, 9-19). Phenotypic correlations between total IQ or performal IQ scores and EEG coherences with and within the prefrontal cortex were low but significant (-.15). The origins of these correlations will be further explored.


Mireille van den Berg1, Eco de Geus1, Dorret I. Boomsma1, Connor V. Dolan2, and Clemens Kirschbaum3
24-hour saliva cortisol measurements in twins and siblings selected to be at high or low genetic risk for anxious depression
1Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands 2Department of developmental psychology, University of Amsterdam, The Netherlands 3Institute of Physiological Psychology II, University of Dsseldorf, Germany
Address: Department of Biological Psychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam The Netherlands Phone: +31 20 4448809 Fax: +31 20 4448832 Email: m.van.den.berg@psy.vu.nl

Multiple factors contribute to the onset of major depression, including a dysregulation of the HPA-axis resulting in high cortisol levels. The purpose of this paper is to: 1) determine whether the relation between heightened cortisol levels and depression is also found in non-clinical samples, 2) examine the nature of this correlation in a genetic design. 309 twins and siblings, ascertained from 160 families registered in the Netherlands Twin Register, participated in saliva cortisol sampling during a 24-hour period. Selection of families is based on a multivariate genetic analysis, on Beck depression, the Young Adult Self-Report, ABV Neuroticism and Spielberger Trait anxiety, derived from a longitudinal study on health and lifestyle. Data of up to 4 repeated assessments, over the period 1991-1997, was available. Subjects were selected to form extreme concordant or discordant sib pairs. In selected offspring, the Composed International Diagnostic Interview (CIDI) was performed, from which DSM-IV diagnosis can be derived. The subjects collected cortisol during a 24-hour period: directly after arrival of the researcher between 9-10 (1st morning sample), 11.00, 15.00, 20.00 and at 22.30. The sixth sample was collected the following morning immediately after awakening. Questionnaire data on general health, health behaviour and mood are available for the measurement day. A normal diurnal rhythm was observed. The high trait depression (htd) group had higher cortisol levels during the day than the low trait depression (ltd) group, according to prediction. However, subjects with a DSM-IV diagnosis had lower cortisol levels than the non-depressed. First analysis suggest that MZ correlations for cortisol are higher than DZ correlations on all measurement points, indicating heritability, save the 1st morning sample. Results of MX modelling will be presented.


Jolande C. van der Valk1,3, Edwin J.C.G. Van den Oord2, Frank C. Verhulst3, and Dorret I. Boomsma1
Genetic and environmental contributions to continuity and change of behaviors at ages 3 to 74
1Vrije Univ, Department of Biological Psychology, Amsterdam, The Netherlands 2Univ of Utrecht, Department of Child and Adolescent Psychology, Utrecht, The Netherlands 3Erasmus Univ, Department of Child and Adolescent Psychiatry, Rotterdam, The Netherlands 4Supported by Sophia Foundation SSWO 165
Address: Vrije Universiteit, Department of Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands Phone: +32 36 333844 Fax: +32 36 331047 Email: Jolande@bhp.be

Objective: A longitudinal psychometric model was used to estimate genetic, shared environmental, and nonshared environmental contributions to the continuity and change in Internalizing and Externalizing Problems at age 3 and 7. Method: Maternal ratings on Child Behavior Checklist questionnaires were collected for 4016 twin pairs at age 3, and four years later for 1924 twin pairs at age 7. Results and Conclusions: Continuity: The continuity of problem behaviors was mostly explained by genetic factors that accounted for 66% and 55% of the stability of Internalizing and Externalizing Problems, respectively. Even though children experience developmental changes, it seems that genetic influences persist during development. Continuing shared environmental influences also mediated the stability of Internalizing and Externalizing Problems over time, accounting for 23% and 38% of the covariance, respectively. This is in accordance to results of epidemiological studies showing that the persistence of factors like family discord and disruption, lack of affection and poor supervision often predict chronic problems. Change: At age 3, genetic factors explained 50% (boys) to 60% (girls) of change in Internalizing Problems. Clear age differences were found, with new genetic factors showing smaller and new shared environmental factors showing larger effects at age 7. For Externalizing Problems no age differences were found. Both at age 3 and 7, new genetic factors accounted for about 40% to 50%, while new shared environmental factors explained about 25% of the change. It thus appears that especially for Externalizing Problems different genes switch on during childhood, and that for Internalizing Problems mostly new familial influences develop. Nonshared environmental factors had very small effects on continuity, with large effects on change of Internalizing and Externalizing Problems. Influences like illnesses or a possible trauma, although certainly not unimportant to children, seem to be of a transient nature of which children appear to recover.


Jacques Vauclair1, and Eric Damerose1
Non human primate patterns of manual laterality
1Centre for Research in Psychology of Cognition, Language & Emotion Universit‚ of Provence
Address: Dr J. Vauclair, Centre for Research in Psychology of Cognition, Language & Emotion, Universit‚ of Provence, 29 avenue Robert Schuman,13621, Aix-en-Provence, France Phone: +33 442953733 Fax: +33 442205905 Email: vauclair@aixup.univ-aix.fr

A survey of manual laterality in non human primate species indicates that patterns of handedness in these species are rather different from the right bias observed in humans. Thus, hand laterality is usually not biased at the population level in nonhuman primates. However, we have shown that laterality is task dependent and recent studies have found a significant right-hand preference in bimanual performance for chimpanzees. The role of genetic and other factors on the determination of handedness will be examined and a possible phylogenetic continuity at least between apes and humans will be discussed.


Richard J. Viken1, Richard J. Rose1, Jaakko Kaprio2, and Markku Koskenvuo3
Genetic and Environmental Transmission of Attitudes toward Alcohol Consumption4
1Department of Psychology, Indiana University 2Department of Public Health, University of Helsinki 3Department of Public Health, University of Turku 4FinnTwin16 is supported by NIAAA (AA 08315 and AA 00145), and by the Academy of Finland (44069) Address: Department of Psychology, Indiana University, 1101 E. 10th St., Bloomington, IN 47405 Phone: 812 855 1697 Fax: 812 855 4691 Email: viken@indiana.edu

Analyses of twin-parent data allow differentiation of genetic and cultural transmission as explanations for parent-child similarity. Thus far, analyses of personality and other individual differences measures have found little evidence for cultural transmission, much to the surprise and disappointment of psychologists and parents. But one domain where we might still expect cultural transmission is in the development of attitudes toward specific objects or activities. In the 2,600 adolescent twin pairs of the FinnTwin16 study, for instance, the pattern of MZ/DZ correlations suggests that shared environment is the predominant source of variation for attitudes toward alcohol consumption (e.g. 'A moderate use of alcohol is part of normal life'; 'Alcohol brings no real happiness to anyone'). Finntwin16 also includes parental data for the same attitudes. The parental data reveal substantial parental similarity for alcohol attitudes, indicating that inferences from the twin data alone may be biased. We fit a variety of parent-offspring models to the data on alcohol attitudes, finding that inferences about genetic versus cultural transmission of attitudes are influenced by both the availability of parental data and the assumptions about the developmental stability of genetic effects and the sources of shared environmental effects made in the underlying models.


Jacqueline M.Vink1, and Dorret I. Boomsma1
Relative risk of smoking parents and smoking siblings on smoking status
1Department of Biological Psychology, Free University of Amsterdam, Van der Boechorstraat 1, 1081 BT Amsterdam
Address: Department of Biological Psychology, Free University of Amsterdam, Van der Boechorstraat 1, 1081 BT Amsterdam Email: jm.vink@psy.vu.nl

The study is part of a longitudinal questionnaire study, that assesses families with adolescent and young adult twins every two year since 1991. The data presented come from the surveys in 1995, 1997 and 2000. The subjects answered questions on health, personality, education, alcohol and smoking. The data on smoking were used to calculate the relative risk for smoking initiation and regular smoking in adolescents with smoking parents or smoking siblings. The relative risk to be a smoker is 4 times higher for adolescents aged between 14 and 16 when they have smoking siblings compared to adolescents with non-smoking siblings. Also, maternal smoking increases the risk to be a smoker in comparison with the mother being a non-smoker (RR=3.03 for boys and 2.73 for girls). The relative risk for smoking initiation (ever smoked) is not elevated for boys (14-16) with smoking parents or siblings in comparison with boys who have non-smoking parents or siblings. In contrast, for girls the risk to start smoking is higher for girls with 1 or more smoking siblings compared to girls who have non-smoking sibs (RR=2.31) and for girls with smoking parents compared to girls who have non-smoking parents (RR=1.75 for smoking father and 1.73 for smoking mother). In 2000 we also collected data on smoking of spouses of twins. The risk to be a smoker is almost 3 times higher when someone has a smoking spouse compared to people with non-smoking spouses. The results show a significant influence of smoking family members on smoking status and smoking initiation of adolescence. Those results cannot distinguish between genetic influences or shared environmental influences. The twin correlations show that smoking initiation both is influenced by genetic and by shared environmental influences.


Jacqueline M.Vink1, and Dorret I Boomsma1
The Fagerströaut;m Test for Nicotine Dependence in a twin-family study
1Department of Biological Psychology, Free University of Amsterdam, Van der Boechorstraat 1, 1081 BT Amsterdam
Address: Department of Biological Psychology, Free University of Amsterdam, Van der Boechorstraat 1, 1081 BT Amsterdam Email: jm.vink@psy.vu.nl

The study is part of a longitudinal questionnaire study, that assesses families with adolescent and young adult twins every two year since 1991. In 2000 a questionnaire on health, personality, alcohol use and smoking was mailed to twins, siblings and spouses of twins. Approximately 3600 subjects had never smoked regularly. The Fagerstr”m Test for Nicotine Dependence (FTND) was filled out by 1572 smokers and 952 ex-smokers. The twin correlations for the FTND are: MZM .55, DZM .23, MZF .68, DZF .31 and DOS .03 which suggests that nicotine dependence is influenced by sex dependent genetic factors. However, the correlation for nicotine-dependence between spouses is as high as the MZ correlation (.50). Correlation between number of cigarettes smoked per day and the score of the FTND is .80 for ex-smokers and .78 for smokers. On the contrary, by selecting heavy smokers (>20 cigarettes a day) still only 30% will have a FTND-score of 7 or higher (range FTND 0: not nicotine dependent to 10: highly nicotine dependent). When selecting subjects who smoke more than 30 cigarettes a day more than 50% will have a FTND score above 7. Nevertheless, the number of subjects who smoke more than 30 cigarettes a day is low: 15 smokers (1% of the smokers) and 25 ex-smokers (2.6% of the ex-smokers).


Sally J. Wadsworth1, Robin Corley1, John K. Hewitt1, Robert Plomin2, and John C. DeFries1
Reading performance at 7, 12 and 16 years of age in the Colorado Adoption Project3: Parent-offspring analyses
1Institute for Behavioral Genetics, University of Colorado, Boulder, CO 2Social, Genetic and Developmental Research Centre, Institute of Psychiatry, King's College London, London, UK 3Supported by grants HD-10333 and HD-18426 from NICHD, and grant MH-43899 from NIMH
Address: Institute for Behavioral Genetics 447 UCB Boulder, Colorado 80309-0447 Phone: 303 492 6795 Fax: 303 492 8063 Email: sally.wadsworth@colorado.edu

The Reading Recognition subtest of the Peabody Individual Achievement Test was administered to children in the Colorado Adoption Project (CAP) at ages 7 (195 adopted and 212 control probands), 12 (197 adopted and 223 control probands) and 16 (181 adopted and 165 control probands), and to their adoptive and nonadoptive parents when the children were 7 years of age. Resulting parent-offspring correlations in adoptive families were not significant at any age, with correlations ranging from -0.12 to -0.03, whereas correlations between scores of nonadoptive control parents and their offspring were significant at all three ages (rPO=0.16 to 0.26). Results obtained from Behavioral genetic model-fitting analyses of the CAP parent-offspring data suggest a trend toward increasing genetic influence with increasing age of the offspring, yielding heritabilities of .41, .46 and .49 at ages 7, 12 and 16, respectively. In contrast, environmental transmission from parents to offspring was negligible, indicating that environmental influences on individual differences in reading recognition are largely independent of parental reading performance. Although G-E correlations were also negligible, assortative mating for reading performance was highly significant (rspousal= .27; p < .001).


Irwin D. Waldman1, Yuki Hadeishi1, David C. Rowe2, Craig Stever2, L. Nicole Giedinghagen3, Jaime M. C. Gard3, Jennifer H. Mohr1, Stephanie Sherman4, and Ann Abramowitz5,
Association of DRD4 and measures of executive functions relevant to ADHD
1Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA 30322 2Division of Family Studies and Graduate Program in Genetics, Campus Box 210033, University of Arizona, Tucson, AZ 85721 3Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721 4Department of Genetics and Molecular Medicine, Emory University, Atlanta, GA 30322 5Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322
Address: mailing address - Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA 30322 Phone: 404 727 7430 Fax: 404 727 0372 Email: psyiw@emory.edu

Phenotype definition has emerged as a critical issue in molecular genetic studies of complex traits. For psychiatric disorders, this may imply augmenting symptom ratings with alternative operationalizations of the disorder of interest. Laboratory measures of relevant cognitive, neuropsychological, or psychophysiological constructs may be useful for expanding the characterization of psychiatric disorder phenotypes. In this study, we examine the use of lab measures of executive functions (EF) as adjuncts to parental symptom ratings in testing for association between the dopamine receptor D4 gene (DRD4) and attention-deficit/ hyperactivity disorder (ADHD). Several studies have demonstrated association and linkage between DRD4 and ADHD. In addition, ADHD is related to a variety of EF deficits, including inattention and impulsivity, and difficulties in organization and planning. In this study, a clinic-referred sample of children (N 100) aged 6 to 16 was genotyped for a 48-bp repeat polymorphism in exon III of DRD4 and administered a battery of EF measures. All of the participants met DSM-IV criteria for ADHD, and many also met criteria for Oppositional Defiant Disorder, Conduct Disorder, and/or internalizing disorders. Following previous studies of DRD4 and ADHD, the 7-repeat allele was considered the high-risk allele. The EF measures included a Continuous Performance Test, the Rey-Osterreith figure, a letter cancellation test, a word fluency test, the Stroop Test of Interference, and Trails A and B. To examine association between DRD4 and each of the EF measures, we regressed participants' EF measure scores on their number of DRD4 high-risk alleles (i.e., 0, 1, or 2). Given that EF measures are often substantially related to age (e.g., accounting for 7% - 43% of the EF variance in this sample), we controlled for age before examining the association between DRD4 and EF measures. DRD4 was associated with performance on a number of EF measures (viz., Rey-Osterreith organization scores, Continuous Performance Task omission errors, word fluency - total words generated and rule breaks, and time to complete Trails A and B) and accounted for 3% - 7% of the variance in these EF measures. These results suggest that association of DRD4 with ADHD is not limited to parents' ratings of DSM-IV symptoms, but also extends to laboratory measures of relevant executive functions. We also discuss the use of these EF measures as adjuncts to symptom ratings in the search for association and linkage between DRD4 and ADHD, as well as how such EF measures may represent useful endophenotypes for ADHD.


Mary Waldron1 and Eric Turkheimer1
A meta-analytic review of bivariate nonshared environment
1Department of Psychology, University of Virginia,Charlottesville, VA
Address: Department of Psychology, P.O. Box 400400, University of Virginia, Charlottesville, VA 22904-4400 Phone 804 243 7630 Fax: 804 982 4766 Email: mwaldron@virginia.edu

Researchers attempting to identify specific nonshared environmentalinfluences have examined almost exclusively the effects of measured differences in sibling environments. Although the concept of nonshared environment originated in behavior genetics, only recently have such studies been conducted using genetically informative samples. When geneticallyinformative samples are available, multivariate genetic models may be used to decompose covariation among environmental and outcome measures into genetic, shared,and nonshared environmental effects. Nonshared environmental sources of environment-outcome covariation represent differences in the measured environment that are systematically related to differences in measuredoutcome and thus provide a test of specific nonshared environmental influences while controlling for genetic effects. In this paper, we report findings from a recent meta-analysis examining the relative contributions of univariate and bivariate nonshared environment. A computerized literature search was conducted to identify empirical studies reporting partitioning of genetic and environmental variance using standard bivariate ACE models (e.g., bivariate cholesky decomposition, and common factor and correlated factor models). Univariate and bivariate estimates of nonshared environment were calculated from reported parameter estimates. Results suggest that although nonshared environment predominates in univariate analyses, in bivariate analyses itdoes not. Moreover, estimates of bivariate nonshared environment are smallestwhen environment-outcome covariation as opposed to outcome-outcome covariation is examined. Discussion of results will focus on implications for research examining systematic sources of nonshared environment.


Hong Xian1, Jeffrey Scherrer2, Pamela AF Madden3,Michael Lyons4, Ming Tsuang5, William R True2, and Seth A Eisen1
Failed Smoking Cessation: Nicotine Withdrawal and Genetic Vulnerability
1VAMC Research and department of Internal Medicine, Washington University 2VAMC Research and St. Louis University School of Public Health 3Department of Psychiatry, Washington University 4Department of Psychiatry, Boston University and Department of Psychiatry, Harvard Medical School 5Department of Psychiatry, Harvard Medical School
Address: Washington University School of Medicine, VAMC 151-JC, 915 N. Grand, St. Louis, MO 63106-1621 Phone: 314-289-6532 Fax: 314-289-7604 Email: hxian@im.wustl.edu

Background: The magnitude of the association between nicotine withdrawal and failed smoking cessation remains uncertain, and the potential genetic contribution to the relationship is unknown. We used a twin design to test if genetic and environmental risk factors contribute to nicotine withdrawal and failed cessation. We then estimated the magnitude of genetic and/or environmental risk factors and their correlations. Methods: Odds ratios for failed smoking cessation as a function of individual nicotine withdrawal symptoms and for severity of withdrawal were computed for 4,112 male twin from the Vietnam Era Twin Registry who responded to a 1992 telephone administration of the Diagnostic Interview Schedule. Genetic model fitting was performed on a sub-sample of 1,808 twin pairs all of whom were lifetime ever smokers and had made at least one quit attempt. Results: After adjustment for cigarette consumption, odds of failed smoking cessation ranged from 0.87(95% CI:0.76-0.99) for 'increased appetite/weight gain' to 1.85 (95% CI:1.55-2.22) for 'depressed'. Odds ratios increased from 1.97 (95% CI:1.55-2.49) to 3.03 (95% CI:2.29-4.00) with increased nicotine withdrawal severity. Genetic influences accounted for 50.0% and 30.7% of the variance in risk for failed smoking cessation and nicotine withdrawal, respectively. The correlation between genetic influences was significant (r=0.38, 95% CI:0.24-0.53). Conclusions: Risk of failed smoking cessation increases with severity of nicotine withdrawal. The risk of experiencing nicotine withdrawal after a quit attempt is partly due to genetic vulnerability, and lifetime risk for both failed cessation and nicotine withdrawal is partly due to genetic factors that are correlated.


Kunio Yamazaki1, Gary K. Beauchamp1, Judith Bard2, and Edward A. Boyse2
Presence of mammary tumor virus alters the body odor of mice
1Monell Chemical Senses Center, Philadelphia PA 19104 2University of Arizona, Tucson, AZ 85724
Address: Monell Chemical Senses Center, 3500 Market Street Philadelphia PA 19104 USA Phone: 215 898 3094 Fax: 215 898 2084 Email: yamazaki@monell.org

It has long been recognized that various genetic and metabolic disorders are characterized by changes in body odor; this is not surprising since many of those conditions alter body chemistry, resulting in an increase or change of odorous substances. We have now found that viral infection, with the Mouse Mammary Tumor Virus (MMTV) prior to any obvious symptoms, alters the body odor of mice. The retrovirus MMTV replicates by reverse transcription of its RNA genome into DNA, leading to chromosomal integration. Since MMTV is characteristically transmitted in the milk, strains of genetically-identical mice can be produced at will by foster nursing. These mice differ only in presence or absence of productive MMTV infection. We first showed that infected (MMTV+) and uninfected control (MMTV-) strains of mice (BALB/cHeA C3H-MTV)were discriminable using our standard Y-maze testing procedure. Next, we selected the MTV- strain to rederive the two lines. Half these offspring were fostered on the MTV+ strain, producing two groups of genetically-identical mice differing only for MMTV infection. These mice, and their urines, were then tested in the Y-maze and were found to be odor-disparate by the 5 trained sensor mice . These studies show that mice could be trained to discriminate female or male intact mice or their urine odors as a function of MMTV infection status. Furthermore, odor distinction based on the presence of virus occurs in the absence of overt disease. The mechanism for this is not currently known.


Susan E. Young1,2, Andrew Smolen1, Michael C. Stallings1, Robin P. Corley1, Thomas J. Crowley2, and John K. Hewitt1
Candidate Gene Studies in Substance-Dependent Adolescents, their Siblings, and Controls 3
1Institute for Behavioral Genetics, University of Colorado, Boulder 2Division of Substance Dependence, University of Colorado Health Sciences Center., Denver 3Funded by NIH grants: DA-05131, DA-11015, HD-10333 and MH-43899
Address: Phone: 303 492 1235 Fax: 303 492 8063 Email: Susan.Young@Colorado.edu

The importance of the dopaminergic system in the development of substance use disorders and related psychopathology is well-established. However, the association between known genetic polymorphisms in a number of dopamine-related genes and substance-related outcomes as well as differences in the frequency of risk alleles in substance abusing versus non-abusing samples remains equivocal. We examine these issues in a sample of 162 substance-dependent youth with comorbid conduct disorder, 222 biological siblings of the patients, and 919 control adolescents consisting of twins, biological and adoptive/unrelated siblings and singletons. Subjects have been genotyped for DAT1, DRD2 and DRD4 and phenotyped using structured psychiatric interviews. We report preliminary evidence for differences in the frequency of risk alleles between groups which may be explained, in part, by ethnic stratification. A formal within-family analysis which i) estimates allelic association for quantitative measures of substance-related problems, and ii) controls for spurious association due to population stratification will be presented.


Patricia Yudkin1, Kate Hey, Sarah Roberts, Sarah Welch, Elaine Johnstone, Michael Murphy, Sian Griffiths, Lesley Jones, and Robert Walton2
Is giving up smoking on the nicotine patch related to genotype?
1Department of Primary Health Care, University of Oxford 2Imperial Cancer Research Fund General Practice Research Group, University of Oxford
Address: Department of Primary Health Care, Institute of Health Sciences, University of Oxford, Old Road, Oxford OX3 7LF Phone: +44 1865 226918 Fax: +44 1865 226720 Email: pat.yudkin@dphpc.ox.ac.uk

There is strong evidence from twin studies for a genetic component to the development and maintenance of tobacco addiction. Published work shows associations between smoking habit and polymorphisms in the dopamine D2 receptor (DRD2 C32806T) and in dopamine beta hydroxylase (DBH G1368A). We hypothesised that these alleles would predict smoking cessation using the nicotine transdermal patch. In 1991-2 we carried out a randomised controlled trial of the nicotine patch on 1685 heavy smokers in 19 general practices in Oxfordshire. The patches were worn for 12 weeks. After one week, the confirmed cessation rates in the nicotine and placebo groups were 32.9% and 21.6% respectively (rate ratio 1.5). At 12 weeks, the cessation rates were 19.4% and 11.8% (rate ratio 1.6). In 1999-2000 we contacted 1532 of the 1612 subjects not known to have died or emigrated. 840 (55%) returned follow-up questionnaires and 755 (49%) gave a blood sample, 378 of whom had received the nicotine patch, and 377 the placebo. We extracted and typed DNA for polymorphisms in DRD2 and DBH, and examined associations between these polymorphisms and smoking cessation in the trial. Smokers carrying alleles associated with increased risk of tobacco dependence showed most benefit from the patch. At one week, the cessation rate ratio was 2.1 for subjects with the DRD2 CT/TT genotype compared with 1.3 for those with CC (p for difference in rate ratios 0.04); 1.7 for subjects with the DBH GA/AA genotype compared with 1.2 for those with GG (p=0.19); and 2.4 for those with both the DBH GA/AA and DRD2 CT/TT genotypes compared with 1.3 for others (p=0.02). At 12 weeks, the rate ratio for subjects with this combination of genotypes was 2.5 compared with 1.4 for others (p=0.07). If confirmed, these results could have important implications for smokers who want to give up by identifying those most likely to gain advantage from the nicotine patch.