Arpana Agrawal1,3, Michael C. Neale1,2,3, Carol A.
Prescott2,3, and Kenneth S. Kendler1,2,3. The influence of early
onset cannabis use on use and abuse/dependence of other illicit drugs:
discordant twin design versus a model-fitting method.
1Department of Human Genetics, Virginia Commonwealth University,
Richmond, VA, 2Department of Psychiatry, Medical College of
Virginia, Virginia Commonwealth University, Richmond, VA, 3Virginia
Institute of Psychiatric and Behavior Genetics, Virginia Commonwealth University,
Richmond, VA
Address: Virginia Institute
of Psychiatric and Behavior Genetics,
Following-up a recent report (M. T. Lynskey,
A.C. Heath, K.K. Bucholz, W.S. Slutske,
P.A. Madden, E.C. Nelson, D.J. Statham, and N.G. Martin, 2003, JAMA, 289(4), 427-33), we used the
discordant twin design to analyze the influence of early onset of cannabis use
on use and abuse/dependence of other illicit drugs. Twins who used cannabis before
the age of 18 years versus non-user co-twins had odds ratios of 2.0-7.5 for
using other illicit drugs. However, the
discordant twin design does not utilize all the available data and has limited
ability to examine the genetic etiology of the relationship between cannabis and
other illicit drug use. Using 1191 male and 934 female same sex twin pairs from
the Mid-Atlantic Twin Registry (K.S. Kendler and,
C.A. Prescott, 1999, Arch. Gen.
Psychiatry, 56, 39-44), we fit three models to our data (M.C. Neale and, Kenneth S. Kendler, 1995,
Am. J. Hum. Genet., 57, 935-953). The correlated liabilities
model most suitably explained the data with a very high correlation of 0.91
between the genetic factors influencing early use of cannabis and other illicit
drug use. A model that only allowed for specific environmental influences to be
correlated (re=0.87) fit poorly. Also, a genetic model of the
gateway hypothesis was not supported. The relationship between early cannabis and
other illicit drug use does not appear to be due to causation at the phenotypic
level (A. Golub and, B.D. Johnson, 1994, J. Stud. Alcohol, 55(5), 607-14) but due
to correlations between factors that influence the individual liabilities.
Thus, prevention of cannabis use may not be successful in curbing use of other
illicit drugs.
Maricela Alarcón1, Rita M. Cantor2, Jussi
Niemi3, Mari Qvarnstrom4, Markku
Ryynanen5, Taisto Leppasaari4, Aarno Palotie2, and Daniel H. Geschwind1. Genomewide scan in Finnish families with dyslexia/dysphasia.
1Department of Neurology, University of
California, Los Angeles CA, 2Department of Human Genetics, University of
California, Los Angeles CA, 3Department of Linguistics, University
of Joensuu, Joensuu,
Finland, 4Department of Otolaryngology, Kuopio
University Hospital, Kuopio, Finland, 5Department
of Obstetrics and Gynecology, University of Oulu, Oulu, Finland
Address: UCLA
Department of Neurology, 710 Westwood Plaza 1-145,
Dyslexia affects approximately 5 to 10% of the population in
the
Juko Ando1 and Yutaka Ono2. Genetic structure of Cloninger's seven factor model revisited.3
1Faculty of Letters, Keio University, Mita
Tokyo, 2Health Center, Keio University, Yokohama Kanagawa, 3Supported
by a Grant-in Aid for Scientific Research(A)from the Ministry of Education,
Science, Sports and Culture
Address: Faculty of
Letters,
Ando et al. (2001, Journal
of Personality, 70,584-609) investigated the genetic structure of R. Cloninger's seven factor model of personality with 296
pairs of Japanese twins with TCI (Cloninger et al.
1993) and revealed that three temperamental dimensions (novelty seeking: NS,
harm avoidance: HA, reward dependence; RD) are genetiucally
independent. The current study is its
replication with larger sample (513 pairs : 330 pairs
of MZs , 116 pairs of same sex DZ, 67 pairs of
opposite sex twins). Univariate
analysis shows that AE model is the best fir for all the dimensions but
self-directedness(SD) and additive genetic contributions are 21% for NS, 45%
for HA, 39% for RD, 34% for PS (persistence) 46% for CO (cooperativeness) and
48% for ST (self-transcendence ). SD can be explained either AE or CE model. Multivariate
analyis by Cholesky decomposition
indicates again that genetic latent factors for three temperamental dimentions are independent.
Andrey P. Anokhin1, Angela Ralano1, and
1Department of Psychiatry , Washington University School of Medicine, St.Louis, MO, 2Supported by grants DA00421-02 from the NIH and CRTG-00-300-01-PBP from the American Cancer society
Address:
Prepulse inhibition (PPI) is a suppression of the startle reflex that occurs when intense startle startling stimulus is preceded by a weaker “prepulse” stimulus. PPI is viewed as an index of sensorimotor gating, a fundamental process of sensory input regulation. PPI deficits have been implicated in the biological bases of schizophrenia and some other neuropsychiatric conditions including substance use disorders and proposed as a possible biological marker ("endophenotype") for genetic studies. However, little is known about the genetic determination of PPI in humans. Accordingly, the purpose of this study was to estimate heritability of PPI in normal human subjects. PPI of acoustic eyeblink startle reflex was assessed in 170 young adult female twins (49 MZ and 36 DZ pairs). Response magnitude was measured as square root of the area under the curve of a rectified, averaged, and smoothed orbicularis oculi EMG signal in the time window of 20-120 ms after stimulus onset. Twin intrapair correlations were significant in MZ (r=0.52, P<0.01), but not in DZ twins (r=0.14, n.s.). Genetic analysis using structural equation modeling showed significant heritability of PPI, suggesting that about 50% of the PPI variance is determined by genetic factors.
Andrey Anokhin1 and Angela Ralano1.
1Department of Psychiatry, Washington University School of Medicine,
St.Louis, MO, 2Supported by grants
DA00421-02 and 5P50 AA11998-03 from the NIH
Address:
Wisconsin Card Sorting Test (WCST) is one of the most widely used assessments
of executive functioning related to prefrontal cortex. Performance on the WCST has been suggested to
indicate familial vulnerability to psychiatric disorders characterized by
executive deficits, such as schizophrenia. However, little is known about
genetic and environmental determinants of individual differences in WCST
performance in the general population. A previous study based on a very small
twin sample did not find significant genetic influences (A. Campana,
F. Macciardi, O. Gambini,
S. Scarone S., 1996, Neuropsychobiology 34, 14-17). The present study assessed heritability of
standard WCST scores in a sample of 166 young female twins including 58 MZ and
25 DZ pairs. A computer-administered version of WCST was used. Several WSCT
indices including total number and percent of errors, and the number of perseverative responses showed modest, but significant
heritability ranging from 37 to 46 %, whereas other indices such as the number
of categories completed and failure to maintain set did not show evidence for
genetic influences. The results suggest that selected aspects of executive functioning
measured by the WCST are moderately influenced by genetic factors.
Jessica H. Baker1,
Kyle L. Gobrogge2, and Kelly L. Klump. A Twin Study of Similarities in Self and Co-twin Reports of
Personality.
1Department of Psychology, Michigan State University, East Lansing,
MI, 2Supported by NIH Grant MH 65447
Address: 129 Psychology
Research Building East Lansing, MI 48824 Phone:517 432
9861 Email: klump@msu.edu
Objective: Several studies
have examined the agreement between self and informant ratings of personality
(Ready 2002; Ready & Clark 2002; Hill et al., 1995; Harkness
et al., 1995). However, few studies have
examined the relative influence of genetic factors on similarities of self and
informant reports of personality. Thus,
the purpose of the current study was to examine genetic and environmental
influences on these reports in male and female twins. Method:
Subjects included 228 MZ and 58 DZ male and female twins participating
in the Michigan State Twin Study.
Personality was measured with the Neuroticism, Extraversion, and
Openness to Experience Personality Inventory Revised (NEO-PI-R) (Costa &
McCrae, 1985). Twins completed two
versions of this instrument, the first asking them to rate themselves, and the
second asking them to rate their co-twin. Biometric model fitting analyses were
used to examine genetic and environmental influences on similarities between
self and informant reports. Results: Model-fitting analyses indicated significant
additive genetic and non-shared environmental influences on most of the
NEO-PI-R subscales. Discussion: Findings suggest greater similarity between
self and co-twin reports of personality in MZ relative to DZ twin pairs that
can be accounted for by genetic and nonshared
environmental factors.
Bojan Basrak.
Copulas in QTL mapping.
Eurandom,
Address: Eurandom (TUE),
Detecting linkage of a marker to a quantitative trait locus (QTL)
in human genetics essentially means detecting a connection between genetic
similarity and similarity of phenotypes. The first similarity is typically
measured using the identity by descent (IBD) status and the second one by the
notion of linear correlation. This also holds for the two most popular methods--the
Haseman-Elston regression method and the variance
components likelihood-ratio test. It is well known that the correlation
coefficient is the most natural measure of stochastic dependence (similarity)
in the world of multivariate normal distributions, but it can be less suitable
when the normality assumption is not met. In practical linkage analysis this
means that the methods that are derived on the basis of normality have to be
used with a great care when this assumption is violated. Not surprisingly, this
problem has attracted a lot of attention recently, see
for instance J. Blangero, J.T. Williams, and L. Almasy, 2000, Genet. Epidemiol.
19, S8-S14 or P.C. Sham, J.H. Zhao, S.S. Cherny,
and J.K. Hewitt, 2000, Genet. Epidemiol. 19, S22-S28. The most general way of expressing
statistical dependence between variables is via copulas. We show how this well
established statistical tool can be applied in QTL linkage analysis with a
little extra effort and potentially many benefits. One particular copula,
namely the bivariate normal copula is discussed in
more detail. In particular, we demonstrate how a statistical analysis based on
the normal copula model deals with problems of non-normality that appear in
many practical studies. Finally we demonstrate applicability and usefulness of
this approach by simulation studies.
Daniel M. Blonigen1,
Brian M. Hicks1, Robert F. Krueger1, Christopher J.
Patrick1, William G. Iacono1, and Matt McGue1. Psychopathic Personality
Traits & Externalizing Psychopathology: Etiologic Connections.
1Department of Psychology,
Address: Department of
Psychology 75 East River Rd. University of Minnesota,
Psychopathic Personality (psychopathy)
is defined as a constellation of interpersonal, affective, and behavioral
features. Our recent factor analytic work with the Psychopathic Personality
Inventory (PPI), a self-report psychopathy measure for
non-incarcerated populations, has shown that it is represented by two
orthogonal factors. The first factor (PPI-I) is related to social dominance and
stress immunity, core features of the affective/interpersonal dimension of psychopathy. The second factor (PPI-II) is marked by
negative emotionality and low constraint, and is strongly related to a
dimension of externalizing psychopathology, defined as the covariance among
child and adult antisocial behavior symptoms, alcohol and drug dependence, and disinhibitory personality traits (R. F. Krueger, B. M.
Hicks, C. J. Patrick, S. R. Carlson, W.G. Iacono, and
M. McGue, 2002, Journal
of Abnormal Psychology 111, 411 - 424).
Although the two factors exhibit distinct relations with personality and
behavioral measures, it is not clear if they are etiologically distinct as well.
In this study we conducted a biometric analysis of the relationship between psychopathy and externalizing in a sample of male and
female twins from the Minnesota Twin Family Study. The Multidimensional
Personality Questionnaire was used to index the two PPI factors, and an
externalizing factor was derived from a principal components analysis of
symptom counts of child and adult antisocial behavior, and alcohol, drug, and
nicotine dependence. We performed a Cholesky
decomposition of the PPI factor scores and externalizing to index the amount of
shared variance among the observed phenotypes that is determined by genetic or
environmental contributions. Ultimately,
the results will address the question of whether or not the two phenotypically distinct dimensions of psychopathy
are preferentially linked to the externalizing dimension at an etiologic level.
Stefan M. Brudzynski. Quantitative
parameters of the ultrasonic communication in rats.1
Department of Psychology and Centre for Neuroscience,
Address: Department of
Psychology,
There is ample evidence that ultrasonic calls emitted by rats are
used for intraspecies communication, which plays an
adaptive role in improving chances of individual and group
survival. Ultrasonic calls are emitted
in biologically significant situations and they have acoustic features, which
are not only specifically recognized by the recipients but also contain a
quantitative dimension reflecting the magnitude of the emitter's response. The
goal of the presentation is to review the features of the ultrasonic calls in
search of the acoustic parameters, which could reflect the quantitative aspect
of the rat vocal communication in addition to the commonly recorded rate of
calling. Isolation calls of rat pups have a variable sound frequency and call
duration, and have changing sonographic structure
over time. It has been concluded that the "message" is encoded in one
or more of the alternative sweeps of frequency, which facilitate attending and
retrieval of the pup by the dam. Isolation calls are replaced with age by two
other ultrasonic call patterns. The, so called 22-kHz calls, or alarm calls,
are emitted predominantly in agonistic and other aversive situations. They are
characterized by a relatively constant sound frequency,
and remarkable variability in the duration of single calls. This variability
and the results of pharmacological studies suggest that the quantitative aspect
in the vocal expression of these calls seems to be encoded in the length of
individual calls. Finally, the 50-kHz calls have
been reported in positive, non-agonistic behavioural
situations. They are characterized by a very short and
relatively constant single call duration, and by a variable sound frequency.
Results of the pharmacological studies and the variability of sound frequency
suggest that the peak sound frequency is likely to reflect the quantitative
aspect in the vocal expression in this type of calls.
Susan A. Brunelli. Selective
breeding for an infantile phenotype (rat pup ultrasonic vocalizations): A
window on developmental processes.1,2
Department of Developmental Psychobiology, New York State
Psychiatric Institute & Columbia University, New York NY, 1Supported
by NIMH Grant MH40430, 2Supported by NIMH Grant MH54027
Address:
A series of studies posed two questions: (1) How generations of
selective breeding of rats for high (High USV line) or low (Low USV line)
levels of USV responses at 10 days of age may affect the time course of USV
response development over the postnatal period; and (2) How the development of
other behavioral and psychological traits may have been altered over the same
period in association with changes in the selected trait. Longitudinal and cross-sectional studies of
rat pups from litters of High, Low and Random lines were conducted in which two
cohorts of litters were tested: one at
3, 10 and 18 days postnatal age, and the second at 7, 14 and 21 days. In addition to the USV response to two minute
isolation tests, other isolation-induced behaviors, physical markers of
maturation and measures of thermoregulation were studied. The results support
the idea that the developmental trajectories of High and Low lines have been
altered differently, i.e., the two lines are not mirror images, and
developmental paths are independent of each other.
Tanya Button1,
Anita Thapar2, and Peter McGuffin1. Maternal smoking during
pregnancy and antisocial outcomes in young people.3
1Social, Genetic and Developmental Psychiatry Research Centre, Institute
of Psychiatry, King's College London, 2Department of Psychological
Medicine, University of Wales College of Medicine, 3Supported by MRC
PhD Scholarship
Address: PO 80, Social,
Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry,
King's College London, De Crespigny Park, London, SE5
8AF Phone: +44 (0) 20 7848 0629 Fax: +44 (0) 20 7848 0575 Email: t.button@iop.kcl.ac.uk
Maternal smoking during pregnancy is associated with conduct
problems in young people. One possible explanation for this association is the
effects of the cigarettes on the brain of the developing fetus, and there is evidence
that nicotine exposure affects brain development. An alternative explanation is
that smoking during pregnancy is an index of maternal antisocial behavior, and
offspring conduct problems may result from genetic transmission for the propensity
to antisocial behavior. This study
examines the relationship between maternal prenatal smoking and antisocial
behavior using data from 1896 twins pairs from the
Greater Manchester and Lancashire Twin Registry. Twins behavior and mothers prenatal
smoking habits were analysed using structural
equation modelling.
Two models were fitted. In the first it was assumed that maternal
smoking had a direct environmental effect (the environmental mediation model), whilst
in the second it was assumed that the correlation between conduct disorder and
maternal smoking was mediated via the mothers' genotype (the genetic mediation
model). The results confirmed that
adolescents whose mother smoked during pregnancy scored significantly higher
for antisocial behavior than those whose mothers were non-smokers. This
increased with the number of cigarettes smoked daily. The genetic mediation
model was a slightly better fit than the environmental model calling into
question the frequent assumption that the effects of maternal smoking on later
antisocial behavior in offspring result from direct toxic effects on the
developing fetus.
Michèle Carlier1,2, Charles Cohen-Salmon1,3, Chabane Chérif1, Fatima Marouf
Verray1, Paricia Arechi1, Fabienne Godin1, Franz Sluyter1,4, Brice
Marcet5, Bernard Verrier5, and Pierre L. Roubertoux1,6. Development of congenic
strains for mitochondrial DNA in mice. Implication of mtDNA in pre-weaning development and motor behavior.
1CNRS Génétique
Address: Centre de recherche en Psychologie de la
Cognition, du Langage et de l’Émotion (PsyCLÉ EA 3273), Université de Provence, 29 avenue Robert Schuman,
13624 Aix en
Mammalian mitochondrial (mt) genome that
encodes 13 subunits and specifies 22 tRNAs
and 2 rRNAs is exclusively maternally transmitted.
The implication of the 13 proteins in respiratory chain and ATP synthase has been demonstrated. Their possible impact on
cognitive or other behavioral processes has been previously suspected. As the
number of mtDNA molecules is large per one somatic cell (more than 1,000) the
gene targeting strategy cannot be used to address the implication of mtDNA
genes in cognition. For this reason, we developed congenic
strains for mtDNA. We selected NZB/BlN and CBA/H mice
that carry mtDNA from different origins. We present here the development of this
quartet of congenic strains, controls for mtDNA cross-transfer
and for the isogenicity of the nuclear background. mtDNA modulates
motor development as soon as the pre-weaning period in interaction with nuclear
DNA. This effect persist in adults and an interaction between mtDNA, nuclear
DNA and age is observed for a wide set of motor measurements.
Penny L. Biersach Clark, Carol A. Van Hulle,
Erri Hewitt, and H. Hill
Goldsmith1. Exploring the genetic architecture of social
and non-social fear in infancy.2
1Department of Psychology,
Address: Department of
Psychology,
Many researchers have examined the development of fear in infancy.
The majority of this research has focused on social fear, which has been shown
to be moderately heritable. Additionally, genetic influences account for the
largest portion of the covariation in parent-report
and observed measures of social fear (Goldsmith et al., 1999, Developmental Psychology 35(4),
972-985). Fewer studies have examined the development of non-social fear in
infancy. Recent research suggests social and non-social fear are differentially
related to vulnerabilities for disruption in emotion regulation (Locke&
Goldsmith, 2002, poster presented at ICIS,
R. P. Corley1,
S. E. Young1, M. C. Stallings1, J. K. Hewitt1, A.
Smolen1, and D. Huizinga2. Sibling resemblance for adolescent problem
behavior: National Youth Survey and CADD.3
1Institute for Behavioral Genetics, University of Colorado, Boulder,
CO, 2Institute of Behavioral Science, University of Colorado, Boulder,
CO, 3Supported by grants DA-05131 and DA-11015, HD-10333, MH-43899,
and AA-11949
Address: Institute for
Behavioral Genetics, Campus
The National Youth Survey (D. S. Elliott, D. Huizinga,
and S. Menard, 1989, Multiple Problem
Youth: Delinquency, Drugs and Mental Health Problems.
Danielle M. Dick1,
Richard J. Viken1, Jaakko Kaprio2,
Lea Pulkkinen3, & Richard J. Rose1. Parents: The
Anti-Drug? Clarifying the role of
parental influence on adolescent smoking and drinking using data from
FinnTwin12.4
1Department of Psychology, Indiana University, Bloomington IN, 2Department
of Public Health, University of Helsinki, FINLAND, 3Department of
Psychology, University of Jyvaskyla, FINLAND, 4FinnTwin12
is supported by NIH (AA 12502), and by the Academy of Finland.
Address: Department of
Medical and Molecular Genetics, Indiana University School of Medicine,
In 1998, the White House Office of National Drug Control Policy
launched the National Youth Anti-Drug Media Campaign, an initiative that has
emphasized the role parents can play in preventing their adolescents from using
drugs. We sought to better clarify the
influence of parents on their adolescents' substance use using data from a
longitudinal twin-family study on the development of smoking and drinking
patterns across adolescence. The sample
for this study, FinnTwin12, consists of five consecutive birth cohorts of
Finnish twins, born 1983-1987. Twins
were assessed with questionnaires at ages 11-12 and reported on several aspects
of their relationship with their parents, such as the amount of time spent
engaged in activities with their parents, and the degree to which their parents
monitor their behavior. The twins were
reassessed at age 14, at which time they reported on their use of cigarettes
and alcohol. Nearly all measures of
parental relations at age 12 predicted smoking and drinking behavior at age
14: children who spent more time with
their parents, reported more parental monitoring and a better home atmosphere
were less likely to be smoking or drinking at age 14. However, twins' reports of parenting were
under a modest degree of genetic influence, as were their substance use
patterns at age 14. Therefore, to
clarify the role of genetic and environmental influences on the relationship
between parenting and substance use, we fit bivariate
models to reported parental supervision and smoking/alcohol use. For all measures of parenting and substance
use, shared genetic influence could be dropped from the model. This suggests that the association between
perceived parenting and substance use is not confounded by a shared genetic
liability. Genetically informative twin
designs provide a useful method for differentiating these developmental
influences.
Brian D_Onofrio1,
Eric Turkheimer1, Robert Emery1, Jane Mendle1, Stacy Lynch1,
Wendy Slutske2, Andrew
Heath3, Nick Martin4. Association Between Parental Divorce and Offspring Life Transitions: Selection or Causation?
1Department of Psychology, University of Virginia, Charlottesville,
VA, 2Department of Psychological Science, University of Missouri,
Columbia, MO, 3Department of Psychiatry, Washington University, St.
Louis, MO, 4Genetic Epidemiology Section, Queensland Institute of
Medical Research,
Address: Psychology
Department, University of Virginia, 102 Gilmer Hall, PO Box 400400,
Charlottesville, VA 22904-4400, Phone: 804-982-4750, Email: briand@virginia.edu
Previous research has shown that children of divorced parents are
more likely to initiate harmful behaviors at younger ages and engage in
untraditional family transitions than children from intact households. However, the causes underlying these
associations are unclear. Genetically
informed designs, including the Children of Twins design, help delineate the
possible genetic and environmental processes that account for the association
between parental characteristics and child outcomes. In order to disentangle
the relation between parental divorce and life transitions in the offspring, a
longitudinal study of twins and their adult children was utilized. The sample
included 2,554 offspring from 889 twin pairs from the Australian Twin Registry.
Results indicated that children from divorced families started to use alcohol,
drink heavily, smoke cigarettes, try marijuana, and engage in sexual
intercourse at earlier ages than children from intact families. They were also
more likely to have a child before they were 18, live with a cohabiting
partner, and experience marital separation themselves. Genetically informed analyses revealed that
environmental processes within nuclear families that are associated with
parental divorce accounted for the relations. Shared genetic factors and
environmental factors which influence twin families could did not mediate the
intergenerational associations.
Cathy Fernandes1,
Jose Paya-Cano1, Frans Sluyter1,
Ursula D'Souza1, Robert Plomin1, and Leonard C. Schalkwyk1. The power of gene
expression profiling and mouse models to unravel behaviour.
1Social, Genetic and Developmental Psychiatry Research Centre,
Address: Social, Genetic
and Developmental Psychiatry Research Centre, PO 82, Institute of Psychiatry,
King's College London, De Crespigny Park, London SE5
8AF, U.K. Tel: +44(0)207 848 0279 Fax: +44(0)207 848 0801 Email spjgcaf@iop.kcl.ac.uk
Understanding the genetic component of complex traits such as
behaviour has long been a formidable task as it has been difficult to study
multiple genes and their products in a single system. Gene expression profiling using microarrays is an exciting new technology that can take a
snapshot of the simultaneous gene expression across thousands of genes. The mouse is an excellent model for such
functional genomics research as there is considerable genetic overlap with
humans, behavioural phenotypes have been well
characterized and a great deal of genomic information is available. Moreover,
both genes and environment can be manipulated or controlled in mice, which
makes it possible to study the relationship between genes and environment at
the level of gene expression. I will
present data on a study comparing hippocampal gene
expression profiles across eight different inbred mouse strains (A/J, C3H/HeJ,
FVB/NJ, DBA/2J, C57BL/6J, Balb/cByJ, 129S1/SvImJ and
SJL/J) using the Affymetrix GeneChip
system. I will focus on the ways in
which the microarray data can be analysed
to identify novel candidate genes and potential gene interactions, using
examples of gene expression profiles that replicate previous findings and those
that nominate novel candidate genes in this study. The potential of using a range of inbred
strains of mice for quantitative analysis of genetic and environmental
influences on gene expression profiles will be considered.
Tom A Fowler1,
Jane Scourfield1, Anita Thapar1, and Anne Farmer2. Does Disabling Fatigue in
Children & Adolescents Share Common Genes with Depression?
1Department of Psychological Medicine,
Address: Department of
Psychological Medicine, University of
Medicine,
INTRODUCTION: Due to the
overlap of symptomology between chronic disabling
fatigue and depression it has been suggested that Chronic Fatigue Syndrome (K.
Fukuda, S.E. Straus, I. Hickie, et al. 1994, Annals of Internal Medicine, 121, 953-9)
is simply a form of depression. A twin method has been employed to examine
whether chronic fatigue and depression in adolescence overlap in terms of
genetic aetiology. METHOD: A screening questionnaire for lifetime ever
disabling fatigue was completed by the parents of 1457 twins, aged 8-17 years, identified
from the
Amber L. Gahagan1 and Irwin D.
Waldman1. Pubertal Maturation
differences in Genetic and Environmental Influences on Conduct Disorder.
1Department
of Psychology,
Address: Department of Psychology,
Theories of the
development of antisocial behavior have posited greater genetic influences and
lesser environmental influences on early- as compared with late-onset
antisocial behavior. In this study, we
examine the effects of pubertal maturation (PM) on the genetic and
environmental influences on Conduct Disorder (CD) in children and adolescents. The participants were twin pairs from the
Georgia Twin Registry, a registry of all multiple births recorded in the state
birth records of
Jody M. Ganiban1. Mothering and Adolescent Externalizing Behavior:
A Behavioral Genetic Exploration.2
1Department of Psychology, The George Washington University, Washington,
DC, 2The Swedish Twin Mothers Project was supported by a grant from
the NIMH (R01 MH54610, PI: Dr. David Reiss)
Address: Department of
Psychology, The
20052. Telephone: (202) 994-7571 Fax: (202) 994-1602 Email: ganiban@gwu.edu
Previous research indicates that distal family-level factors such
as marital dissatisfaction and parents’ mental health are related to
adolescents’ behavior problems, and that these associations are mediated by
parenting style. Although these findings are well-established, the mechanisms
that account for them are less clear. This paper will examine the degree to
which associations between distal family factors and maternal negativity are
explained by genetic and environmental factors. Additionally, exploratory
analyses will examine whether associations between family factors and
adolescents’ externalizing behaviors are best explained by passive genetic
transmission or by evocative gene-environment processes. Data from the Swedish Twin Mothers Project
will be presented (Reiss, D., Cederblad, M.,
Pedersen, N., et al, 2001, Family Process,
8, 40, 261-272). This study included female twins, their partners, and
their children. The sample consisted of 150 MZ and 176 DZ female twin pairs
(mean age = 44 + 4.5 years), and 552 children (322 male cousins, and 330 female
cousins; average age = 15 + 2.2 years). Self-report measures were used to
assess the women’s depressive symptoms, marital dissatisfaction, and parenting
style. Mothers also rated their adolescents’ externalizing behaviors. Factor
analyses were used to create composite scores for marital dissatisfaction and
maternal negativity towards her child. Preliminary
analyses indicate that maternal depressive symptoms and marital dissatisfaction
contribute to maternal negativity through different channels: while genetic factors primarily explained
associations between depressive symptoms and maternal negativity, associations
between marital dissatisfaction and maternal negativity were explained by nonshared environment factors. Exploratory analyses will capitalize upon the
inclusion of adolescent cousins who vary in genetic relatedness in this study,
and estimate the degree to which associations between maternal
negativity and adolescents’ externalizing behaviors are explained by the
passive transmission of genes from mother to child, or by the adolescents’
unique genetic makeup.
Heather L. Gelhorn1,
Michael C. Stallings1, Susan E. Young1, Robin P. Corley1,
John K. Hewitt1, Thomas J. Crowley2. A Detailed Investigation of DSM-IV Conduct
Disorder Symptoms: Heritability of Individual Items and a Comparison of
Selected and Unselected
Samples.3
1Institute for Behavioral Genetics, University of Colorado, Boulder,
CO, 2Dept. of Psychiatry, U. of Colorado Health Sciences Center, Denver,
CO, 3Supported by NIDA grants DA-05131, DA-11015, DA-12845
Address: Institute for
Behavioral Genetics, Campus Box 447 University of Colorado,
Research on antisocial traits from twin and adoption studies has consistently
implicated genetic factors in the etiology of conduct disorder (CD). However
few studies have looked at individual symptoms to determine the extent to which
these behavioral problems may be genetically or environmentally influenced. Additionally, researchers frequently employ case-control
designs where CD symptoms are compared between selected samples and unselected
controls. Such strategies assume that the selected cases simply represent the
extremes of an underlying distribution that is shared with the controls. There has been very little research to
directly support this assumption. The
current study uses both patient and community-based adolescents participating
in the Center for Antisocial Drug Dependence at the
Kyle L. Gobrogge1
and Kelly L. Klump1. Homosexual Mating Preferences from an
Evolutionary Perspective.2
1Department of Psychology,
Address:
Objective: Several studies
have examined mating behavior from an evolutionary perspective in both
heterosexual and homosexual male populations (Silverthorne & Quinsey, 2000; Bailey et al., 1994; Jankowiak
et al., 1992; Freund et al., 1973).
These investigations have shown that both heterosexual and homosexual
men prefer younger partners compared to heterosexual women. However, most studies relied on
laboratory-based assessments that required subjects to hypothesize about their
preferences and did not specify what types of relationships were desired for
each preference. The purpose of the present
study was to examine these issues naturalistically by comparing partner
preferences of homosexual and heterosexual men who placed internet personal
advertisements. Method: Subjects included 338 homosexual and 265
heterosexual men placing internet personal ads on lavalife.com in each of the
50 states in the
to replicate the current findings.
Detre A. Godinez1, Michael C. Stallings1, Susan
E. Young1, Robin P. Corley1, John K. Hewitt1. Investigating Genetic and Environmental
Influences on Age at Onset of Alcohol Use and the Latency from First Use to
Regular Use in the
1Institute for Behavioral Genetics,
Address: Institute for
Behavioral Genetics, Campus Box 447 University of Colorado,
Although there is a considerable body of literature investigating
genetic and environmental influences on drinking patterns, much less is known
about the determinants of age at initial alcohol use and how quickly one progresses
from initial use to higher levels of use. The current study investigates the genetic and
environmental influences on age of alcohol initiation, age of regular (at least
monthly) use, and the latency between initiation and regular use in an adolescent
sample. Participants were 567 monozygotic
and 598 dizygotic twin pairs between the ages of 12
and 18, drawn from a community based twin sample (Colorado Twin Registry). Two analyses were conducted. First, we used complete data where both twins
had: 1)initiated
use; 2)progressed to regular use; or 3)reached both use milestones—for the
transition latency analysis. Age of onset was treated as a continuous variable
and was corrected for age trends in the sample. In a second analysis we used
methods described by Pickles et al. (1994, Behav. Genet.,
24, 457-468), allowing for censored cases (i.e., that some adolescents have not
yet initiated use or progressed to regular use). Results of analysis-1 indicated moderate
heritability for age at first use, age at regular use, and the transition
latency. Among twins who had both initiated
use (ignoring monthly use status), shared environmental effects were estimated
at approximately 20%. However, among
twin pairs that had progressed to monthly use there was little evidence for
shared environmental influences for age of onset or the transition latency. Results of analysis-2, utilizing all of the
twin data, confirmed moderate heritability for age at initiation and age at
monthly use, but suggested the importance of shared environmental effects
(estimated at approximately 30%). Additional survival analyses will examine the
transition latency and potential telescoping effects due to retrospective
reporting.
Julia D. Grant1
and Kathleen K. Bucholz1. Early alcohol use as a risk factor for later
alcohol dependence: Genetic and
environmental influence and overlap.2
1Department of Psychiatry,
Address:
Adolescent behaviors such as alcohol use have the potential to
impact adult development. The present analyses use data from a sample of
Vietnam-era veteran male twin pairs to examine genetic and environmental
contributions to early alcohol use, and how early use relates to adult alcohol dependence. Data from 3,452 twin pairs (MZ=1,923;
DZ=1,529; mean age=41.9 years) who participated in a 1992 telephone diagnostic
interview for the Vietnam Era Twin Study (VETS) were analyzed. Eighty-nine percent (n=6,112) of the
respondents had used alcohol regularly (i.e., at least once a month for 6+
months). Age of onset for regular
drinking (M = 18.4 years) was used to create a 6-level age of use variable
(with never drinkers included as the "latest onset" category). Additionally, lifetime alcohol dependence
(AD) was assessed using DSM-III-R criteria; 40% of regular drinkers met AD
criteria. Structural equation modeling
(using Mx) indicated that age of onset for regular
alcohol use was heritable, with genetic influences explaining 34% of the
variance (95% CI = 22-46). Shared environmental
influences were also significant, explaining 15% of the variance (95% CI =
5-25). Nonshared
environmental influences explained 51% of the variance (95% CI = 47-55). AD was also heritable, with genetic influences
accounting for 52% of the variance (95% CI = 34-58). Shared environmental influences on AD were
non-significant, explaining 1% of the variance (95% CI = 0-17); nonshared environmental influences accounted for 47% of the
variance (95% CI = 41-53).
Interestingly, the overlap between the two measures was almost entirely
attributable to genetic influences: the
genetic correlation of -0.71 (95% CI = -0.54 to -0.97) indicated that 50% of
the genetic variance in AD was overlapping with genetic influences on age of
onset for regular alcohol use. Neither
the shared environmental nor the nonshared
environmental correlation was significant.
Guang Guo, Glen Elder, and
Nathan Hamilton. Role of Peers,
Heritability, & Adolescent Drinking.
Department of Sociology,
Address: Department of
Sociology, CB# 3210, UNC,
Using same-sex twin and sibling data from the National longitudinal
Adolescent Health Study based in the
Haberstick, B.C., Schmitz, S., Young, S.E., and Hewitt, J.K. Individual differences in
behavioral problems as rated by different teachers across middle childhood and
early adolescence.
Institute for Behavioral Genetics,
Address: Institute for
Behavioral Genetics, Campus
In the current study, we report findings from the first large
scale longitudinal twin study of siblings rated by different teachers. We examined teacher ratings on the Teacher
Report Form (TRF, Achenbach, 1991b) collected across six ages during middle
childhood and early adolescence for a large sample of monozygotic (MZ) and dizygotic (DZ) twin siblings in different classrooms. As an index of enduring characteristics of a
child, we took an average of these observations for each of the 358 MZ (194
girls and 164 boys) and 310 DZ twin siblings (144 girls and 166 boys). For these averaged scores, boys, on average,
were rated as having more social, thought, and attention problems, as well as displaying
more delinquent, aggressive, and overall externalizing behaviors than
girls. Furthermore, MZ twins were rated
as more similar than DZ twins on each of the behavioral and broadband scales on
the TRF. Univariate
model fitting to observed individual variances and pair covariances
was conducted in order to estimate the genetic and environmental contributions
to individual differences in problem behavior within gender. Heritability estimates were found not to
differ between girls and boys and ranged between 54% and 61% for overall
externalizing behaviors and its behavioral scales while ranging between 27% and
73% for overall internalizing behaviors and its behavioral scales. Individual differences in stable attention
and social problems were also found to be
strongly heritable across six years of observations, with estimates of 67%
and 61%, respectively. Environmental
influences shared by members of a twin pair did not show a significant
influence on any scale. From these findings
we conclude that individual differences in persistent problem behaviors during
middle childhood and early adolescence within the school setting are due to a combination
of genetic contributions and non-shared environmental influences.
Noa Heiman1, Mats Larsson2, Michael C.
Stallings1, Susan E. Young1, Andrew Smolen1, and
John K. Hewitt1. Novelty seeking and
dopamine receptor polymorphisms in adolescence.
1Institute for Behavioral Genetics, University of Colorado,
Boulder, CO, 2Center for Developmental Research,
Address: Institute for
Behavioral Genetics, Campus Box 447,
The importance of genetic contributions to personality traits is
well established, as indexed by moderate heritability estimates found in twin
studies. In addition, several studies
have reported associations for particular variants of the dopamine D4 receptor
gene (DRD4) with the personality trait of novelty seeking. The DRD4 gene has a variable number of tandem
repeats (VNTR) in its third exon, which have been
shown to affect the function of the D4 receptor efficiency in vitro. However, replication studies have shown mixed
results. The aim of our study was to
investigate whether such an association replicates in a large adolescent
sample. Our sample consisted of 1227
adolescents between the ages of 11 and 19. Adolescents were drawn from the
Colorado Twin Registry, a community-based sample of twins residing in
Brian M. Hicks, Linde Althaus, Robert F. Krueger,
Matt McGue, and William
G. Iacono. Adolescent sexual behavior and externalizing
psychopathology:
Longitudinal, cross-sectional,
and biometric analyses.
Department of Psychology,
Address: Department of Psychology,
Rd.,
Sexual behavior, particularly sexual behavior of a risky or
irresponsible nature, has been linked with substance abuse and tendencies
toward behavioral disinhibition. Previously, we have reported that disinhibitory syndromes, including adult and child
antisocial behavior and alcohol and drug dependence, can conceptualized as a
spectrum of disorders indicative of a broad and highly heritable
psychopathological process called Externalizing (EXT). In this investigation, we sought to delineate
the relations between sexual behavior and various facets of the EXT spectrum using
data from the 11 and 17 year-old cohorts of the Minnesota Twin Family Study. Both sexual behavior and EXT disorders were
assessed via in-person, structured interviews.
For our measure of sexual behavior, we employed a dichotomous variable
for engaging in sexual intercourse as well as a dimensional variable of sexual
behavior that included items covering dating behavior, frequency of sexual
intercourse, fear of being pregnant (or fear of getting someone pregnant), and actual pregnancy (or actually getting someone
pregnant). We conducted longitudinal,
cross-sectional, and biometric analyses.
First, we investigated whether childhood EXT disorders at age 11 (e.g.,
conduct disorder, oppositional defiant disorder, attention deficit hyperactivity
disorder) predicted the emergence of sexual behavior at age 14. Second, we examined cross-sectional
associations between sexual behavior and adult EXT phenotypes (adult antisocial
behavior and substance disorders) at age 17.
Finally, we examined the etiological sources of covariation
between sexual behavior and EXT for both the longitudinal and cross-sectional
analyses.
Robert Hitzemann1,
Cheryl Reed1, Barbara Hitzemann1, Robert W. Williams1,
James Sikela1, Kari Buck1, Jonathan Flint1,
and Christopher Talbot1. On the intergration
of QTL gene expression and sequence analyses.2
1Department of Behavioral Neuroscience, Oregon Health and Science
University, Portland, OR 97239, 2Supported in part by AA11034, MH
51372 and the Vetrans Affairs Medical Research
Service.
Address: Department of
Behavioral Neuroscience Oregon Health Sciences University 3181 SW Sam Jackson
Park Road Portland OR 97201-3098 Telephone: (503) 404-2858 FAX: (503) 494-6877
E-Mail: hitzeman@ohsu.edu
Although hundreds if not thousands of quantitative trait loci
(QTL) have been described for a wide variety of complex traits, only a very
small number of these QTLs have been reduced to
quantitative trait genes (QTGs) and quantitative trait
nucleotides (QTNs). A strategy will described for
detecting QTGs and QTNs that
is based on leveraging the information contained within the haplotype
structure of the mouse genome. The strategy utilizes the 6 F2 intercrosses that
can be formed from the C57BL/6J (B6), DBA/2J (D2), BALB/cJ
(C) and LP/J (LP) inbred mouse strains. Focusing on the phenotype of basal locomotor activity, it was found that in all three B6
intercrosses, a QTL was detected on distal chromosome 1; no QTL was detected in
the other three intercrosses and thus, it was assumed that at the QTL, the C,
D2 and LP strains were identical by descent. These intercross data were used to
form a simple algorithm for interrogating microsatellite,
SNP, brain gene expression and sequence databases. The results obtained point to Kcnj9 (which
has a markedly lower expression in the B6 strain) as being the likely QTG. Further, it is suggested that the lower expression
in the B6 strain results from a polymorphism that disrupts the binding
of at least 3 transcription factors - Ikaros 1, MZF1
and C/EBPbeta.
For these factors, the homology of the binding site motif to that found
in Kcnj9 was highest for Ikaros 1 and poorest for C/EBPbeta .
Overall, the method described should be widely applicable to the analysis of QTLs.
Yoon-Mi Hur. Two decades of assortative
mating for education in
Address: Graduate of
Education,
Assortative mating affects heritability estimates in twin and family studies
because it increases genetic resemblance between first-degree relatives. Recently increasing numbers of twin studies
on the basis of Asian samples have been published. Degrees of assortative
mating in Asian samples, however, are little known. The present study examined assortative mating for educational attainment in
N Jacobs1, F
Rijsdijk2, C Derom3,4, M Danckaerts5,
1Department of Pyschiatry and Neuropsychology, Maastricht University, European Graduate
School of Neuroscience, P.O. Box 616, 6200 MD Maastricht, The Netherlands, 2Social, Genetic &
Developmental Psychiatry Research Centre, Institute of Psychiatry, London SE5
8AF, United Kingdom, 3Center for Human Genetics, Catholic University
Leuven, Herestraat 49, 3000
Leuven, Belgium, 4Association for Scientific
Research in Multiple Births, Kwadenplasstraat 12,
9070 Destelbergen, Belgium, 5Department of
Child Psychiatry, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven,
Belgium, 6Department of Psychiatry and Neuropsychology,
University Ghent, De Pintelaan 185, 9000 Ghent,
Belgium, 7Division of Psychological Medicine, Institute of
Psychiatry, De Crespigny Park, London SE5 8AF, United
Kingdom
Address: Dept. Psychiatry
and Neuropsychology,Section Social Psychiatry and Psychiatric
Epidemiology Maastricht University, P.O. Box 616, 6200 MD Maastricht, The
Netherlands Phone: +31-43-3299785 Fax:
+31-43-3299708 Email: nele.jacobs@sp.unimaas.nl
Previous work has demonstrated associations between lower cognitive
ability and childhood and adult non-psychotic psychopathology. As both
cognitive ability (CA) and child psychopathology (CP) are influenced by genetic
factors, one explanation for the association is that they are the pleiotropic manifestations of the same underlying genetic
factors. The present paper examines three possible causes of the association:
additive genetic factors, common environmental factors and individual-specific environmental
factors. 376 twin pairs from the East
Flanders Prospective Twin Survey were examined with the Child Behaviour
Checklist and the Wechsler Intelligence Scale for Children-Revised. The
cross-twin within-variable, within-twin cross-variable and cross-twin
cross-variable correlations were calculated. Using structural equation modelling, bivariate models were
fitted. The best fitting model was chosen, based on likelihood and parsimony. The observed phenotypic correlation between CP
and CA was -0.19 (95% CI:-0.09,-0.27), with genetic factors accounting for
about 84% of the observed correlation. Bivariate
model fitting quantified the genetic correlation between CP and CA at -0.27
(95% CI:-0.12,-0.42) and the individual-specific environmental correlation at
-0.17 (95% CI: -0.03,-0.31). In children, three different genetic factors
may exist: one that solely affects the liability to CP, one that has only an
effect on CA and one that influences both CP and CA. While individual-specific
environmental factors can influence the liability to both traits, our results
suggest that most of
the environmental factors that increase the risk of CP do not
influence CA and vice versa.
N
Jacobs1, I Myin-Germeys1, L Krabbendam1, C
Derom2,3, and J van Os1,4. Do genes
make people feel blue after stress? An experience sampling twinstudy.
1Department of Pyschiatry and Neuropsychology, Maastricht University, European Graduate
School of Neuroscience, P.O. Box 616, 6200 MD Maastricht, The Netherlands, 2Center
for Human Genetics, Catholic University Leuven, Herestraat 49, 3000 Leuven,
Belgium, 3Association for Scientific Research in Multiple Births, Kwadenplasstraat 12, 9070 Destelbergen,
Belgium, 4Division of Psychological Medicine, Institute of
Psychiatry, De Crespigny Park, London SE5 8AF, United
Kingdom
Address: Dept. Psychiatry
and Neuropsychology,Section Social Psychiatry and Psychiatric
Epidemiology Maastricht University, P.O. Box 616, 6200 MD Maastricht, The
Netherlands Phone: +31-43-3299785 Fax:
+31-43-3299708 Email: nele.jacobs@sp.unimaas.nl
People show different emotional responses to stressors.This
study examined to what degree individual differences in emotional reactivity to small daily
life stressors could be explained by genetic and/or environmental factors. 152 female twin pairs (99 MZ and 53 DZ)
participated in an Experience Sampling study (ESM). ESM is a structured diary
technique used to assess stressors and mood at 10 random times for 5
consecutive days. An increase in
self-reported subjective stress was associated with an increase in negative
affect and a decrease in positive affect. For each subject, the stress-induced
increase in negative affect and decrease in positive affect was
calculated. Structural equation modelling was applied to these variables. The best fitting model
was chosen, based on fit and parsimony. For the stress-induced decrease in positive
affect, the best fitting model was the model with a common environmental
factor, explaining 19% of the variance (95%CI 0.03-0.34) and an
individual-specific environmental factor, explaining 81% of the variance (95%CI
0.66-0.97). For the stress-induced
increase in negative affect, the best fitting model was the model with a
dominant genetic factor, explaining 35% of the variance (95%CI 0.17-0.51) and
an individual-specific environmental factor explaining 65% of the variance
(95%CI 0.49-0.83). This was the first
study ever to examine the role of genes and environment in emotional reactivity
to daily stressors. It was found that i)stress-induced increase in negative affect was influenced
by genetic and environmental factors, ii)stress-induced decrease in positive
affect was influenced only by environmental factors.
Kristen C. Jacobson1,
Andrew Crider2, William S. Kremen3, Hong Xian4,
Brian Waterman4, Seth A. Eisen4, Ming T. Tsuang5,
and Michael J. Lyons6. Genetic and environmental
influences on electrodermal lability
and its association with antisocial behavior.
1VIPBG, Department of Psychiatry, Virginia Commonwealth University,
2(emeritus) Department of Psychology, Williams College, 3Department
of Psychiatry, UC Davis, 4School of Medicine, Washington University
in St Louis, 5Harvard Institute of Psychiatric Epidemiology and Genetics,
Harvard University, 6Department of Psychology, Boston University
Address: VIPBG; Department
of Psychiatry,
The present study used data from 345 twin pairs from the Alcohol Vulnerability
Study to examine genetic and environmental influences on three measures of skin
conductance response (SCR): SCR lability during rest,
number of trials to habituation, and SCR lability
during a digit transformation task situation. Participants were male-male twins
aged 41-58 from the Vietnam Era Twin Registry. Although the three variables were
highly correlated ( r = .57-.70), and univariate
analyses revealed heritabilities of ~ .40 for each of
the three variables, multivariate analyses indicated that there were
significant genetic influences on the measures that were unrelated to genetic
influence on the underlying latent trait. Specifically, 30% of the total heritabilities for trails to habituation and SCR lability during task were due to genetic influences not
shared with the other measures. Only a small proportion (8%) of the genetic
influence on resting SCR lability was not shared with
genetic influence on the latent trait. Variation in the latent trait was due
approximately equally to genetic and nonshared environmental
influences. Common environmental influences were not significant. These results
indicate that genetic factors play an important role in accounting for
variation in an underlying latent phenotype that is defined by related measures
of SCR. However, there are additional genetic factors that influence variation
in individual measures of SCR, especially SCR sensitivity and SCR during task situations.
Further analyses will examine the extent to which these three measures of SCR
are related to conduct-disordered and adult antisocial behaviors, and will
additionally examine the extent to which these associations between SCR and
antisocial behavior are influenced by common genetic factors.
Jang, K.L.1,
Dick, D.M.2,
1Department of Psychiatry, University of British Columbia, Canada, 2Department
of Psychology, University of Indiana, USA, 3Department of
Psychiatry, University of California—San Diego, USA
The study tested for evidence for gene-environment interplay on
the development of personality dysfunction:
specifically environmental control of genetic expression and
experiential moderation of preexisting environmental conditions. A battery of continuously measured
psychosocial stressors was assessed in three independent samples of twins (141,
194, and 86 MZ pairs and 129, 184, and 77 DZ pairs, respectively) who reported
on the environment of the childhood home, parental bonding, traumatic events
and traits delineating personality disorder.
Genetic moderator path models evaluated the magnitude of heritable and
non-heritable effects on personality function across levels of each of the
psychosocial variables. Results showed
evidence for gene-environment interaction but most of the psychosocial
variables tested impacted on the environmental conditions influencing
personality function.
Wendy Johnson, Matt McGue, and William G. Iacono1. Disruptive behavior and school achievement:
Genetic and environmental relationships in 11-year-olds.2
1Department of Psychology,
Address: Department of
Psychology,
There is a well-established association between conduct problems
and attentional problems. In addition, there is a
well-established association between conduct problems and poor academic
achievement including school drop out. Several studies (e.g. D. M. Fergusson
and L. J. Horwood, 1995, Journal of Abnormal Child Psychology, 23, 183-199) have concluded,
however, that, in the absence of attentional
difficulties or below average IQ, conduct difficulties are not associated with
later difficulties with academic achievement. This has largely been based on
observations of clinic-referred males of high school age. Using the
population-based Minnesota Twin Family Study, we investigated the relationships
among conduct and attentional problems, IQ, and
academic achievement in 11-year-old males and females. Following development of
appropriate sex-specific phenotypic models, we investigated the genetic and
shared and nonshared environmental influences on the
relationships observed.
Wendy Johnson and Robert
F. Krueger1. Genetic and environmental structure of the
big 5 personality traits in a national twin sample.2
1Department of Psychology,
Address: Department of
Psychology,
Using a nationwide sample of 275 same-sex dizygotic
and 315 monozygotic twin pairs from the National Survey of Midlife Development
in the United States (MIDUS), we investigated the etiologic basis for the
phenotypic coherence of the five domains (Extraversion, Neuroticism,
Agreeableness, Conscientiousness, and Openness) of the Big Five Model of
personality. We compared multivariate
models specifying varying degrees of latent phenotypic structure and estimating
genetic and environmental structural influences among adjectives describing
each of the Big Five personality domains. Results showed both common and
specific genetic and environmental influences for each domain, suggesting that
all of the domains are etiologically complex. In addition, the models
specifying the domains as latent phenotypic constructs fit more poorly than
models specifying less coherent structure, particularly for Openness and
Agreeableness. These results raise questions about the BFM as an explanatory
model of personality or, alternatively, about the etiological unity of latent
phenotypic personality trait constructs in general.
Kenji Kato1,2 and Nancy L. Pedersen1,3. Personality and coping: A study of twins
reared apart and twins reared together.4
1Department of Medical Epidemiology, Karolinska
Institutet, Stockholm, Sweden, 2School of
Health Science, Faculty of Medicine, Osaka University, Osaka, Japan, 3Department
of Psychology, University of Southern California, Los Angeles, CA 90089, 4Supported
by National Institute on Aging Grants AG-04563 and AG-10175
Address: Kenji Kato, Dept.
of Medical Epidemiology, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden Email: Kenji.Kato@mep.ki.se
This study aimed to explore the genetic and environmental factors influencing
stress coping styles, age and gender differences, and the relationship between
coping and personality in middle-aged and older adults, as part of the ongoing
Swedish Adoption/Twin Study of Aging (SATSA). SATSA participants in the third
questionnaire wave (58 MZ and 147 DZ twin
pairs reared apart, and 101 MZ and 140 DZ twin pairs reared together;
the mean age was 61) were given the Billings and Moos Coping Measure. Three
meaningful factors were derived from factor analysis and termed ‘Problem
Solving,’ ‘Turning to Others,’ and ‘Avoidance.’ For
the purposes of these analyses, Neuroticism and Extraversion from the EPI and
Openness to Experience
from the NEO-PI were included. Univariate model
fitting showed additive genetic influences for the coping scales (variance
components ranged 16-56%). Turning to Others and
Avoidance indicated gender differences in the relative importance of genetic
and environmental influences. The best-fit models contained only additive genetic
and nonshared environmental factors except Turning to
Others for women, which also had shared rearing environmental influences. No age
differences were found in this sample. Multivariate model fitting showed
substantial genetic contributions to the phenotypic correlations in the
associations between Problem Solving and Openness to Experience, between
Turning to Others and Openness to Experience for women, and among Avoidance,
Extraversion, and Neuroticism for women. The findings suggest that genetic
influences on adults' coping are differentially mediated by genetic factors in
common with personality traits.
Kelly
L. Klump1, Matt McGue2, and William G. Iacono3. Puberty
and eating pathology: Shared genetic effects.
1Department of Psychology, Michigan State
University, East Lansing MI, 2Department of Psychology, University
of Minnesota, Minneapolis MN, 3Supported by NIH Grants MH 65447, DA
05147, AA 09367
Address:
Previous research has found significant increases in rates
of clinical eating disorders as well as disordered eating characteristics (K.L.
Klump, M. McGue, and W.G. Iacono, in press, Int J Eating Disorders)
in girls following puberty. Recent findings suggest this increase may be due to
genetic factors, as genetic influences on weight preoccupation and overall
disordered eating appear to be greater in pubertal than pre-pubertal girls (K.
L. Klump, M. McGue, and
W.G. Iacono, in press, Int J Eating Disorders). The
purpose of the present study was to directly examine this possibility by
investigating shared genetic effects between puberty and these disordered
eating characteristics in a population-based sample of female twins. Participants included 276 fourteen year-old
female twins from the Minnesota Twin Family Study. Disordered eating was measured with the
Minnesota Eating Disorders Inventory (M-EDI) (K. L. Klump,
M. McGue, and W. G. Iacono,
2000, J of Abn
Psychology, 109, 231-251), while pubertal status was measured with the
Pubertal Development Scale (PDS) (A.C. Petersen, L. Crockett, M.
Laura B. Koenig1,
Matt McGue1, Robert F. Krueger1, and Thomas J. Bouchard, Jr.1. Examining the relationship between
religiousness, prosocial and antisocial behavior:
Genetic versus environmental mediation.
1Department of Psychology,
Address: Department of
Psychology,
River Road,
Although religiousness is considered a major protective factor
against the expression of substance abuse and other antisocial behavior, it
remains unclear whether these associations are primarily genetically or environmentally
mediated. In order to investigate this
and related issues, religiousness was assessed by self-report in a sample of
adult male twins (169 MZ pairs and 104 DZ pairs, mean age of 33 years). Twin correlations for retrospective reports
of religiousness in adolescence showed little difference between MZ (r=.69) and
DZ (r=.59) twins. Twin correlations for reports
of current level of religiousness, however, did show stronger MZ (r=.62) than
DZ (r=.42) similarity. Biometric
analysis of the two religiousness ratings revealed that genetic factors were
significantly weaker (12% vs. 44%) and shared environmental factors were
significantly stronger (56% vs. 18%) in adolescence compared to adulthood. Nonetheless, both current and adolescent
religiousness independently contributed to the prediction of adult antisocial
and prosocial behavior. Results from a joint biometric analysis of
religiousness and antisocial and prosocial behavior,
undertaken to determine whether the relationships among these
variables were genetically or environmentally mediated, will be presented.
Sulev Kõks1,
1Department of Physiology, University of Tartu, Estonia, 2Department of Psychiatry,
University of Tartu, Estonia, 3Institute
of Molecular and Cell Biology, Tartu, Estonia, 4Asper
Biotech Ltd., Tartu, Estonia, 5 Supported
by Estonian Science Foundation Grants 4562, 4614, 5528
Address: Department
of Physiology,
Phone: +372 7 374 335 Fax: +372
7 374 332 Email: Sulev.Koks@ut.ee
Mood disorders are among the most prevalent forms of mental
illnesses. Depression and bipolar disorder are both highly heritable disorders,
with genetic factors comprising roughly 50% of the risk for depression and as
much as 80% of the risk for bipolar disorder. Linkage studies have focused on
genomic regions containing putative candidate genes involved in various
neurotransmitter systems. Weak associations have been reported between depression
and several single nucleotide polymorphisms, but results are inconsistent. The
aim of the present study was to find possible associations between the most
extensively studied polymorphisms and unipolar or
bipolar affective disorder. Patients with panic disorder were also involved in
this study. We genotyped 128 SNPs
from altogether 22 genes with Arrayed Primer Extension (APEX) technology.
The SNPs included in our study cover several
neurotransmitter systems (serotonin, dopamine, opioid
and cholecystokinin) and additionally one plausible
candidate gene with unknown function – wolframin. We
recruited 150 healthy controls, 105 patients with unipolar
disorder, 108 patients with panic disorder and 38 patients with bipolar
disorder. All subjects were interviewed with M.I.N.I. and SSP tests. We found
that several putative SNPs were not polymorphic at
all. Evidence for significant association was established for some SNPs. In addition, some SNPs were
positive with both unipolar and bipolar disorder
group, other SNPs were disorder-specific – positive
association was established only with a respective group of patients. We found
positive association in patients with panic disorder for SNPs
in the CCK, CCK2R, POMC, PENK, 5-HT1A and 5-HT1B genes. Positive
associations were established in patients with unipolar
depressive disorder for SNPs in the CCK1R,
TPH, DRD1, DRD2, PENK, mu-opioid receptor genes and wolframin gene. Patients with bipolar depressive disorder
had positive associations with the SNPs in the wolframin, DRD4, delta-opioid
receptor and mu-opioid receptor genes.
Robert F. Krueger and
Wendy Johnson1. Sense of Control, sociometric
status, and health: genetic and
environmental connections.2
1Department of Psychology,
Address: Department of
Psychology,
Given the robust finding that people in higher SES groups tend to
experience better physical health, there has been interest in identifying
psychosocial variables that are related to health and may help to explain the
social class health gradient. Sense of control of one_s
life is one variable that has been identified as filling a possible moderating
role. Lachman and Weaver (M. E. Lachman
and S. L. Weaver, 1998, Journal of
Personality and Social Psychology, 74, 763-773), for example, found that,
though control was related to health across all income levels, those low SES
individuals who expressed a high sense of control experienced levels of health
comparable to those of individuals of higher SES. Using a nationwide sample of
twin pairs from the National Survey of Midlife Development in the United States
(MIDUS), we fit a series of biometric models including multivariate and
environmental moderation models in an attempt to unravel the genetic and
environmental bases of these relations.
Henrik Larsson1, Henrik
Andershed2, and Paul Lichtenstein1. Genetic
and environmental influences on the psychopathic personality constellation.
1Department of Medical Epidemiology, Karolinska
Institutet, Stockholm, Sweden, 2Department
of Behavioural, Social and Legal Sciences, Örebro University, Örebro Sweden
Address: Box 281, SE-171 77
Individuals with a psychopathic personality constellation differ
from other antisocial youth in terms of age of onset, the number of violent
acts committed, the seriousness of their offenses, as well as violence while institutionalized.
Little is known about the etiology of this personality constellation, even
though a strong genetic effect often is assumed. The aim of this study was to investigate the
importance of genetic and environmental influences on the relationship among
the three dimensions (grandiose/manipulative, callous/unemotional, impulsive/irresponsible) of the psychopathic personality
constellation in adolescence. Data from
the Swedish Young Twins study, comprised of 1090 twin pairs (aged 16-17 year), was used. The psychopathic personality constellation
was measured with a self-report questionnaire (The Youth Psychopathic traits
Inventory; YPI). We used a
common pathway model hypothesizing that the covariation
between the YPI- dimensions is determined by a latent phenotype (i.e.,
psychopathic personality constellation). The results suggested that the psychopathic
personality constellation is highly heritable (a2 = .63). The shared
environmental factor on the latent phenotype was estimated to zero. Significant unique genetic influences were
found in the callous/unemotional and in the impulsive/ irresponsible dimension,
but not in the grandiose/manipulative dimension. These results suggest that the three
dimensions are subsumed under a higher order factor (i.e., psychopathic
personality constellation), with a strong genetic influence.
Maria J. Lavooy1
and Martin E. Hahn2. A review of the methods of
studies on maternal retrieval and infant ultrasonic vocalization in small
rodents.
1Department of Psychology, University of Central Florida, Cocoa, FL,
2Department of Biology, William Paterson University, Wayne, NJ
Address: Department of
Psychology,
Infant rodents produce at least three sounds that serve as signals
regulating aspects of infant-adult interactions. Of those three, pure ultrasonic
vocalizations have been the most studied since their discovery in the late
1950's. Most investigations conclude that ultrasonic vocalizations and
olfactory cues are the basis of maternal retrieval of pups that are found
outside the nest and thus are critical to the survival of pups who are poor thermoregulators. While ultrasonic vocalizations and their developmental
time course are currently the focus of several types of investigation,
questions remain about the role of ultrasonic vocalizations in mother-infant interactions.
The purpose of this paper is to review the literature on small rodent
ultrasonic vocalizations and on maternal retrieval, with a focus on methods
employed. In the ultrasound section, we will catalog the stimulus conditions
used to elicit ultrasonic vocalizations and the results achieved. In the maternal retrieval section, we will
focus on the settings in which pup retrieval has been studied and the role of
genotype and other maternal variables as the sources of differences in
retrieval performance. We hope that the results of this review will assist in
two areas. First, we hope to clarify the relationship between ultrasonic
vocalizations and maternal retrieval. Second, we hope to recommend some sets of
standardized conditions for the elicitation of ultrasonic vocalizations so that
studies on the effects of psychoactive drugs will have a common basis.
Lisa N. Legrand, Matt McGue, Margaret
Keyes, Steve Malone, and William G. Iacono. Do Rural Environments
Constrain the Genetic Expression of Externalizing Psychopathology?
Department of Psychology,
Address: Dept. of Psych., U
of MN, Elliott Hall,
The relative contribution of genetic and shared-environmental
influences to alcohol use has been shown to vary by environmental
circumstances, with higher heritability reported in urban settings (D.M. Dick,
R.J. Rose, et al., 2001,<I> J. of Abnormal
Psych.</I>, 110, 625-632). We
sought to replicate this gene-environment interaction with a
Jeffrey M. Lessem1,
Christian Hopfer2, Andrew Smolen1, John K. Hewitt1. Genetic Analysis of Antisocial Behavior and
Drug Abuse in the Add Health Study.
1Institute for Behavioral Genetics, University of Colorado, Boulder,
2Div. of Subst. Dependence, Univ. of Co.
Health Sciences Ctr.,
Address: Institute for
Behavioral Genetics, 447 UCB,
Add Health uses a school based design to assess health related information
on adolescents in grades 7-12. Subjects
were interviewed twice, about one year apart, between 1994 and 1996, creating
Waves I and II. Wave III of data
collection was undertaken six years later, and will be ready in 2003. Of the large amount of information collected
as part of the Add Health study, this investigation is examining antisocial
behavior and drug related behavior.
Genotyping of several candidate loci, including dopamine transporter, serotonin
transporter, the dopamine D4 and D2 receptors, and monoamine oxidase-A is currently underway. As a preliminary step in performing association
analyses, the antisocial behavior and drug phenotypes are being screened for
genetic and environmental influences.
This study reports the heritability of the relevant phenotypes on
approximately 2100 families, with 200 MZ twin pairs, 400 DZ twin pairs, 1000 full-sibling
pairs, and 350 half-sibling pairs.
Supported by P01-HD31921 (PI: JR Udry).
Paul Lichtenstein1,
Jan-Olov Larsson2, and Henrik
Larsson1. The development of
Attention Deficit Hyperactivity symptoms from childhood to early adolescence.
1Department of Medical Epidemiology, Karolinska
Institutet, Stockholm, Sweden, 2Department
of Child & Adolescent Psychiatry, The Karolinska Hospital,
Stockholm, Sweden
Address: Box 281, SE-171 77
Attention Deficit Hyperactivity Disorder (ADHD) has shown considerable
genetic effects in both childhood and adolescence. The core symptoms of ADHD
may persist into adolescence and early adulthood, but could also diminish in
severity over time. It has been reported that the rate of ADHD decline by 50%
approximately every 5 years. There are no reports on how genetic and
environmental effects change over puberty.
We have studied continuity and change of ADHD symptoms in a nation wide
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. Sex-limitation models indicated that different
sets of genes were important for the sexes. Genetic effects accounted for about
65% of the variation in ADHD symptoms in both boys and girls at both time
points. There was little evidence for
shared environmental effects. In both genders, correlations for ADHD symptoms
between age 8-9 and age 13-14 were around 0.50. About 80% of the stability in
symptoms was due to genetic effects. Genetic and nonshared
environmental effects contributed about equally to change. The strong genetic influences on the
stability of ADHD symptoms suggest that persistence of ADHD might mediate
genetic effects to adult psychopathology. The new genetic effects in
adolescence could be due to hormonal changes during puberty. The relatively
strong new nonshared environmental influences in
adolescence suggest that changes in the environment could be beneficial in the
prevention and treatment of ADHD.
John C. Loehlin1. Parents and their children: How alike are
they in personality and attitudes, and why?
1Department of Psychology,
Address: Department of
Psychology A8000,
A search of the literature revealed 1279 published parent-child
correlations from 59 studies since the 1930s.
The tabulation was limited to correlations based on at least 50 pairs,
and to Western societies. Mean
correlations were compared for three types of parent-child pairs: (1) pairs
related both genetically and socially, i.e., parents and children from ordinary
families; (2) pairs related only socially, i.e., parents and children in
adoptive families; and (3) pairs related only genetically, i.e., parent and adopted-away
child or MZ and twin's child.
Comparisons were made for personality traits versus attitudes and
interests; for older and younger children; across the "Big Five"
personality domains; and for different pairings by sex--fathers with sons,
mothers with daughters, etc. The results
suggested that most of the fairly modest parent-child resemblance in personality,
attitudes, and interests reflects shared genes, although there is a small
social contribution for attitudes, and young children's personalities appear to
have an appreciable social component.
Resemblances were similar across the Big Five, and across different sex
combinations in the case of attitudes; in the case of personality, resemblance
appeared to be somewhat more social for fathers and children, somewhat more
genetic for
mothers and children.
1
Department of Zoology and Hydrobiology, University of Tartu,
Tartu, Estonia, 2 Department of
Physiology, University of Tartu, Tartu,
Estonia, 3 Supported by Estonian Science Foundation Grant 4562
Address:
The aim of the present study was to identify differentially expressed genes in the rat amygdala in response to exposure to cat odor. Cat odor was used to induce ethologically relevant anxiety reaction in male rats (J. Panksepp, 1998, Affective Neuroscience: the Foundations of Human and Animal Emotions, Oxford University Press, New York). The differential expression of genes was analyzed using cDNA Representational Difference Analysis (cDNA RDA) (M. Hubank and D.G. Schatz, 1999, Methods. Enzymol. 303, 325-349). Products of substractive hybridization (differentially expressed transcripts) were cloned and identified by sequencing and database search. From 576 sequenced clones 67 unique differentially expressed transcripts were identified. The results were subsequently confirmed by dot-blot analysis. According to their function the transcripts can be classified as neurotransmission related, metabolic enzymes, cell cycle regulating proteins, and transcription factors. This report provides preliminary clues for understanding the molecular basis of anxiety. Additional quantitative analysis of expression levels of the identified transcripts is needed to verify the present results.
Stacy
Lynch1, Jane Mendle1, Brian D’Onofrio1, Robert
Emery1, Eric Turkheimer1, Wendy Slutske2,
Andrew Heath3, Nick Martin4. Marital Status and
Depression.
1Department of Psychology, University of Virginia,
Charlottesville, VA Supported by William T. Grant Foundation, Grant
#2054, 2Department
of Psychological Science, University of Missouri, Columbia, MO, 3Department
of Psychiatry, Washington University, St. Louis, MO, 4Genetic
Epidemiology Section, Queensland Institute of Medical Research, Brisbane, QLD,
Australia
Address: Dept. of
Psychology,
Phone: (434) 982-5573 E-mail: akl8t@virginia.edu
Several studies have considered the relationship between depression and marital status. Findings in this area have illustrated that interpersonal discord influences depressive symptoms. What remains unclear is whether depression is a precursor or a byproduct of relational discord. One strategy to address such questions involves the utilization of twin data. Using longitudinal data from the Australia Twin Registry, a number of bivariate models will be fit in an effort to understand the direction of the association between depression and martial status and the gender differences in that relationship. Examining 277 MZ and DZ twin pairs discordant for divorce on the outcome of depression will also help to unravel the genetic and environmental processes which account for this relationship.
Michael T Lynskey. Early onset
risky behaviors and risk for substance dependence: A latent class approach.
Missouri Alcoholism Research Center, Department of Psychiatry,
Washington University School of Medicine, St Louis, MO 63108
Address: Department of
Psychiatry, Washington University School of Medicine, 40 N. Kingshighway,
Suite One,
Early life transitions, including early substance use and early school
leaving often co-occur and are also associated with increased risks for the
development of substance dependence and mental health problems. To examine the extent to which associations
between these transitions could be modeled as a function of a smaller number of
latent classes a series of latent class models were fitted to data on these transitions
using the program LCAP. Data was
collected on 6265 young
adult Australian twins (median age = 30 years) including retrospective reports
of early transitions (early onset substance use behaviors, precocious sexual
activity and role transitions, including early school leaving and leaving the
parental home) and lifetime rates of substance abuse and dependence. There was a moderate degree of association
between these measures of early transitions and latent class analyses
identified a four class model for both males and females. These classes
corresponded to: a) a group with low probabilities of all transitions (60.2%
males, 58.8% females); a group with elevated probabilities of tobacco use and early
school leaving but not of the other transitions (18.2% males 11.4% females); c)
those with elevated probabilities of early substance use and sexual activity
only (18.5% males; 28.6% females); those with elevated
probabilities of all transitions (3.1% males, 1.1% females). After control for retrospectively assessed
measures of CSA, conduct disorder and other childhood disadvantages, those most
prone to early transitions had odds of substance dependence, major depression
and suicidal behaviors that were 1.8 to 11.4 times higher than individuals with
low probabilities of these transitions.
It is proposed that the processes linking these early transitions to
later risks are likely to be social in origin.
Hermine H. Maes, Patrick F. Sullivan, Cynthia Bulik, Michael C. Neale, Carol A.
Prescott, Lindon J. Eaves, and Kenneth S. Kendler1. Genetic analyses of smoking initiation,
regular smoking and nicotine dependence.2
1Virginia Institute for Psychiatric & Behavioral Genetics,
Department of Human Genetics and Psychiatry, Virginia Commonwealth University,
Richmond VA 23298, 2Supported by NIH grants HL60688, MH45268,
AA06781, AA07728, AA07535, MH40828, RR08123 and MH01458
Address: VIPBG, MCV/VCU,
Understanding the contribution of genetic and environmental
influences to the various stages of smoking initiation to more severe forms of smoking
behavior (regular smoking, smoking persistence, nicotine
dependence) is an important first step in finding specific etiological factors
for smoking. We examined the
relationship between genetic and environmental risk factors for smoking
initiation, regular smoking, smoking persistence and nicotine dependence in
twins from the population-based Virginia Twin Registry. The smoking variables were assessed in
female, male and opposite sex twin pairs by personal interview. Model fitting results indicated that the
liabilities for smoking initiation, regular smoking and smoking
persistence/nicotine dependence were highly related, but did not lie on a
single distribution of liability.
Although variance components could be equated across zygosity
or gender without significant loss of fit; thresholds could not. The contribution of shared environmental
factors was not significant.
Heritability for smoking initiation was estimated at 75%. About a quarter of the heritability for
liability to regular smoking was explained by genetic factors independent of
those influencing initiation. The
liability to smoking persistence was primarily accounted for by genetic factors
(h<sup>2</sup>=.66). As much
as 26% of the variance in liability to persistence was due to genetic factors specific
to smoking persistence. These results
were similar to those for liability to nicotine dependence (24%) and the Fagerstrom Test for Nicotine Dependence (FTND, 26%). These results suggest that although there
appears to be significant overlap between the genetic factors involved in
starting to smoke and continuing to smoke, they may be genes specific to
smoking addiction.
Matt McGue1,
Margaret Keyes1, S. Brent Walden1, and William G. Iacono1. Shared environmental
influences on adolescent functioning: Parent and sibling effects.2
1Department of Psychology,
Address: Department of
Psychology 75 East River Rd. University of Minnesota,
Research has consistently shown that two domains of adolescent
adjustment, problem behavior and intellectual ability, run counter to the
general finding of minimal shared environmental influence on psychological outcomes. Unclear is whether these shared environmental
influences reflect parent effects or common exposure to other environmental
factors. The Sibling Interaction and
Behavior Study (SIBS) was undertaken to identify and characterize shared
environmental influences on adolescent adjustment. We will report findings from the first 325
adopted and 120 biological sibling pairs to participate in SIBS. We find significant sibling similarity, both
adopted and biological, on a latent factor of adolescent problem behavior that
loads on delinquency, negative peer models, substance use, and substance abuse/dependence. Further, sibling similarity on this phenotype
is moderated by sibling similarity in age and gender, such that like-sex siblings
who are near in age are much more similar than unlike-sex siblings who are
distant in age. We contrast these
findings with results for intellectual ability, where there is significant
adopted and biological sibling similarity that is not moderated by sibling
gender or age difference. We conclude
that the nature of the shared environmental influences differ in the two
domains, with sibling effects being more salient for adolescent problem
behavior and parent effects being more salient for intellectual achievement.
Jane Mendle1,
Brian M. DOnofrio1, Stacy K. Lynch1, Eric N. Turkheimer1,
Robert E. Emery1, Wendy Slutske2, Andrew C. Heath3,
and Nicholas G. Martin4. Association
of paternal absence with age of menarche.5
1Dept. of Psychology, University of Virginia, Charlottesville VA, 2Department
of Psychological Science, University of Missouri, Columbia, MO, 3Department
of Psychiatry, Washington University, St. Louis, MO, 4Genetic
Epidemiology Section, Queensland Institute of Medical Research, Brisbane, QLD,
Australia, 5Supported by William T. Grant Foundation, Grant # 2054
Address: Dept. of
Psychology,
Phone: (434) 982-5573 E-mail:
jemendle@virginia.edu
Early onset of menarche is associated with increased risk for
intercourse. Since cognitive and
physical development do not necessarily occur at the same rate, precocious
sexual maturation increases the likelihood that girls will be forced to
confront new environments, stressors, and social expectations before they are
psychologically prepared to do so. In
recent years, theorists have offered an evolutionary, environmental explanation
for early menarche, linking it with paternal absence in the home. Girls raised either by single mothers or by
mothers and stepfathers are primed to undergo physical maturation at an earlier
age. Although posited as an environmental
consequence of family stress, this association could be mediated by genetic
pathways. Girls begin menstruating at
roughly the same age as their mothers began menstruating. Rowe (2002) has estimated the heritability of
menarcheal age to be .50. Therefore, the relationship between early
menarche and paternal absence might be an artifact of genetic
associations. Since early menarche is
associated with early sexual intercourse and consequent single motherhood, it
seems possible that mothers predisposed to raise children without a biological
father present bequeath an early menarcheal age to
their daughters. One way of clarifying
the genetic composition of menarche is through the children-of-twins
design. If the association between
menarche and paternal absence is actually a by-product of genetic influences,
the age of menarche in children of discordant twins will be comparable --
despite the differing environmental circumstances in which these cousins were
raised. Using data from the Australian
Twin Registry, this analysis will be accomplished through a series of
hierarchical linear regressions modeling age of menarche at an individual,
nuclear family, and twin family level.
Elizabeth A. Molloy1,
Jonathan Blumenthal1, Liv S. Clasen1, Alex
Zijdenbos2, Judith L. Rapoport1, and Jay N. Giedd1. Brain Morphometry and IQ in Pediatric Monozygotic Twins.
1Section on Brain Imaging, Child Psychiatry Branch, NIMH, Bethesda,
MD, 2Montreal Neurological Institute, McGill University, Montreal,
Quebec, Canada
Address:
Magnetic Resonance Imaging (MRI) studies have shown a modest
correlation between brain size and general intelligence. As part of an ongoing study of the effects of
genes and environment on normal pediatric brain development we sought to
explore the relationship between brain morphometry
and IQ within monozygotic (MZ) twins. Thirty-five
sets of MZ twins ages 6.03 to 18.45 (mean age = 12.9, s.d.
= 3.27) underwent MRI on the same GE 1.5 Tesla scanner. Subjects were administered the Wechsler
Abridged Scale of Intelligence (WASI).
Quantitative analysis of cortical gray matter volume was performed using
the Montreal Neurological Institute automated method. Spearman rank correlations showed that
within-pair differences in IQ were positively correlated with differences in
Total Cerebral Volume (TCV) (r = 0.35, p < 0.05). Differences in IQ were positively correlated
with differences in Total White Matter (r = 0.42, p < 0.01). After controlling for TCV, differences in IQ
were negatively correlated with differences in Total Gray Matter (r = -0.37, p
< 0.05). Within-pair differences in
TCV were related to differences in birth weight (r = .33, p < 0.01);
however, differences in IQ were not related to differences in birth weight (r =
.16, n.s.). Birth order was not associated with TCV
or IQ. Understanding the relationship
between pediatric brain changes and behavior changes is a fundamental objective
of neuroscience and may shed light on the nature, pathophysiology,
and treatment of neurodevelopmental disorders. Our results suggest that non-genetic
influences play a role in brain/IQ relationships, and may indicate that general
intelligence is associated with developmental changes (increased myelination and gray matter pruning) known to occur in late
childhood and adolescence. The relationship between brain size and IQ during
childhood and adolescence appears to be influenced by environmental factors not
accounted for by birth weight or birth order.
Brian S. Mustanski1,
Richard J. Viken1, Jaakko Kaprio2,
Torsten Winter2, and Richard J. Rose1. Multivariate
Behavior Genetic Analyses of Sexual Health.
1Department of Psychology,
Address: Indiana University
Department of Psychology,
The field of human sexuality has received little attention from
behavior geneticists relative to such areas as personality, psychopathology,
and substance abuse. That is
unfortunate, because behavior genetic research can enhance understanding of the
relative contribution of specific social, psychological, and biological
influences that have been identified as important predictors of sexual health.
For example, adolescents represent one of the fastest-growing risk groups for
HIV in the
Michael C. Neale1. A finite mixture distribution approach to the
analysis of twin data.2
1Virginia Institute for Psychiatric & Behavioral Genetics,
Department of Psychiatry,
Address: VIPBG, MCV/VCU,
The analysis of data collected from a classical twin study of
monozygotic (MZ) and dizygotic (DZ) twins depends
upon accurate diagnosis of zygosity. However, large scale surveys frequently
resort to questionnaire-based methods of diagnosis which classify twins as MZ
or DZ with less than perfect accuracy, and in some cases no information on zygosity is available at all. This paper describes a mixture distribution
approach to the analysis of twin data when zygosity
is not perfectly diagnosed. Estimates of
the probability that each pair is MZ (p(MZ) or DZ
(p(DZ)) are used to obtain a weighted conditional likelihoods of the form p(MZ)
L(data|MZ) + p(DZ) L(data|DZ).
The performance of this method is compared to fully accurate diagnosis, and to
the analysis of samples that include some misclassified pairs. Even for rates
of misclassification as high as 15\%, the method shows relatively little loss
of precision of estimates of proportions of variance due to additive genetic,
common environment and specific environment sources. However, considerable bias in parameter estimates
is observed when misclassification is ignored, such that additive genetic
variance is underestimated while common environment and to a lesser extent
specific environment components are overestimated. These biases are eliminated with the mixture
distribution approach.
Jenae M. Neiderhiser1.
Genetic and Environmental Influences on Change and Continuity in Family
Relations from Adolescence to Young Adulthood.2
1Center for Family Research, Department of Psychiatry and
Behavioral Sciences,
Address:
Few studies have examined relationships among family members from
adolescence to adulthood, and fewer still have employed genetically sensitive
designs. Current research indicates that
genetic and shared environmental factors influence parent-child relationships
during childhood and adolescence, and that genetic and nonshared
environmental factors influence marital relationships during middle adulthood.
The current study will examine associations among middle and later adolescent
parent-child relationships and young adult relationships with their parents and
with their romantic partners. Subjects
from the Nonshared Environment in Adolescent
Development (NEAD) project will be used for the current report. NEAD included
720 families consisting of two parents married at least 5 years in nondivorced and step families with two siblings (< 4
year age difference). Average child age at Time 1 was 13.6 (+3) years and 15.0
(+2) years at Time 2. There were five types of sibling pairs: MZ and DZ twins,
full, half and step siblings. Measures
included in these analyses index parent-child relationships as rated by
mothers, fathers, adolescent self-reports and observer ratings for each parent’s
behavior towards each adolescent. A follow-up of the NEAD sample is just being
completed. The now young adult participants range in age from 23 to 31 years
and over 90% are married, cohabitating or involved in an exclusive romantic
relationship. Measures for this study include young adult and parent reports of
current adult child-parent relationship and young adult reports of current
romantic relationship quality. We expect
parent-child relationships from adolescence to young adulthood to show high
levels of stability although the pattern of genetic and environmental
influences should change over time. Specifically, shared environmental
influences on parent-child relationships should decrease from adolescence to
young adulthood. The expectations for the correlation between parenting and
young adult relationships are less clear both phenotypically
and in terms of genetic and environmental influences.
Jenae M. Neiderhiser1.
The Impact of Antisocial Behavior on Young Adult Parent-Child Relationships:
Genetic and Environmental Influences.2
1Center for Family Research, Department of Psychiatry and Behavioral
Sciences,
Address:
In the early 1980's David Rowe published some of first work in "environmental
genetics" by looking at genetic and environmental influences on parenting
in a sample of adolescent twins. This work inspired a generation of researchers
to consider this sort of question and to attempt to understand its relevance
for child and adolescent adjustment. In the current paper this question has been
taken to a different level in that genetic and environmental
influences on longitudinal associations between adolescent antisocial
behavior and young adult parent-child relationships are considered. Subjects from the Nonshared
Environment in Adolescent Development (NEAD) project will be used for the
current report. NEAD included 720 families consisting of two parents married at
least 5 years in nondivorced and step families with
two siblings (< 4 year age difference). Average child age at Time 1 was 13.6
(+3) years and 15.0 (+2) years at Time 2. There were five types of sibling
pairs: MZ and DZ twins, full, half and step siblings. Measures included in
these analyses index parent-child relationships as rated by mothers, fathers, adolescent
self-reports and observer ratings for each parent's behavior towards each
adolescent. A follow-up of the NEAD sample is just being completed. The now
young adult participants range in age from 23 to 31 years and over 90% are
frequent (approximately once/week) contact with their parents. Measures for
this study include young adult and parent reports of current adult child-parent
relationship. Preliminary analyses have
confirmed a phenotypic correlation between adolescent antisocial behavior and
young adult-parent relationships. We expect that this association will be due
primarily to genetic influences common to both adolescent antisocial behavior
and young adult-parent relationships.
Michele L. Pergadia1,
Andrew C. Heath1, Nicholas G. Martin2, and Pamela A.F. Madden1. Genetic
Analyses of DSM-IV Nicotine Withdrawal.
Medical Research Council.
Address: Department of
Psychiatry, Washington University School of Medicine, 40 N. Kingshighway,
Suite One,
Less is known about the genetic influences on nicotine withdrawal
relative to other smoking related behaviors. This study examined whether there
are genetic influences on nicotine withdrawal, and whether there are genetic factors
specific to nicotine withdrawal, after controlling for experimentation with
cigarettes and lifetime regular smoking (at least weekly smoking). Data were
obtained by telephone diagnostic interview in 1989 with 6257 individual
Australian twins (3454 women, 2803 men; mean age=30). Analyses of relative
genetic and environmental influence on nicotine withdrawal were surprising.
Genetic modeling of nicotine withdrawal using the entire sample, including
never smokers, fit the data well [Chi sq: 4.6, p=.80; A: 46% (23-55), C: 0%
(0-17), E: 54% (45-64)].Restricting the sample to only pairs where both twins
at least experimented with cigarettes, resulted in a good fitting model and no substantial
reduction in genetic influence on nicotine withdrawal [(Chi sq: 4.8, p=.85; A:
42% (18-52) C: 0% (0-17), E: 58% (48-69)]. However, when we used only pairs
where both twins have a lifetime history of regular smoking, genetic influences
on nicotine withdrawal were substantially reduced [(Chi sq: 5.1, p=.82; A: 30%
(0-43) C: 0% (0-27), E: 70% (57-85)],although familial
influences remained significant. Preliminary results from fitting a two stage
genetic model (first dimension of liability: regular smoking-second dimension
of liability: DSM-IV nicotine withdrawal) suggested that genetic influences on
nicotine withdrawal partially overlap with genetic influences on lifetime
regular smoking, providing little evidence for genetic influences specific to
withdrawal.
Carol A. Prescott, Jonathan
W. Kuhn, and Kenneth S. Kendler. Adolescent problem behaviors and risk for
alcoholism: A causal association?
Virginia Institute for Psychiatric and Behavioral Genetics,
Department of Psychiatry,
Address: VIPBG, VCU,
Risk for alcoholism is increased among individuals who begin
drinking at an early age. In a prior paper (C. A. Prescott and K. S. Kendler, 1999, Alc: Clin Exp Res, 23, 101-107, we
reported that this association was familial in origin and suggested that early drinking
is a vulnerability indicator rather than a direct cause of problematic alcohol
involvement. In the present study we examined the association between
alcoholism and other indicators of adolescent problem behavior, including
conduct disorder, school dropout, and early use of tobacco and illicit
drugs. METHODS - Lifetime DSM-IV alcohol
abuse/dependence (AAD) and five indicators of problem behavior (early use of
alcohol, tobacco and illicit drugs, conduct disorder symptoms, and school
dropout) were assessed in 1,958 women and 3,523 men aged 18 to 64 from same-sex
twin pairs in the Virginia Twin Registry.
RESULTS - AAD was significantly associated with each of the problem
behavior indicators in males and all but school dropout in females. Alcoholism
in both males and females was predicted about equally well by early smoking and
early drug use as by early drinking. Results
from twin pair analyses indicated that the majority of this association arose
because these problem behaviors and AAD share familial (probably genetic)
variation. CONCLUSIONS - Alcoholism is preceded
by multiple forms of behavioral deviance during early adolescence. Our finding
that early use of tobacco and drugs predicts the development of alcoholism even
in the absence of early drinking, combined with the evidence from twin analyses
that the covariation between alcoholism and problem
behaviors is due primarily to genetic and familial environmental factors,
suggest that early drinking is a vulnerability indicator rather than a direct
cause of alcoholism.
David C. Rettew1,
William Copeland1, Catherine Stanger1, and James J.
Hudziak1. Associations between
Temperament and DSM-IV Disorders in Children and Adolescents2.
1Department of Psychiatry, University of Vermont
College of Medicine,
Address: University of
Objective: To investigate
associations between child temperament and DSM-IV disorders in children. Method: A total of 156 probands
(97 boys, 59 girls; mean age=10.78) and 154 randomly selected siblings (90 boys
and 64 girls; mean age=10.80) were assessed using the Junior Temperament and
Character Inventory (JTCI) and a structured DSM-IV interview as rated by
mothers. Subjects were placed into non-overlapping
diagnostic groups of 1) attention-deficit/hyperactivity disorder (ADHD) only,
2) disruptive behavior disorders (DBD) only, 3) DBD plus an affective and/or
anxiety disorder (DBD+Int), and 4) controls with no
diagnosis. Statistical analyses
conducted separately with probands and siblings
included analyses of variance and hierarchical logistic regressions. Results:
Many JTCI scales were found to differ between diagnostic groups and
controls. Regression analyses showed
independent associations between low persistence and ADHD-only group
membership, high novelty seeking and the DBD-only group, and between high harm
avoidance, high novelty seeking and low self-directedness, and DBD+Int group membership. The interaction of novelty
seeking X harm avoidance was related to the ADHD-only group. Conclusion:
Psychopathology in children is associated with temperamental
differences, including possible interactions between different temperamental
dimensions.
Sally-Ann Rhea1
and Brett C. Haberstick1. Parenting and Peer Relationships in Early Adolescence:
A twin study replication of adoption study data.2
1Institute for Behavioral Genetics,
Address: Institute for
Behavioral Genetics, Campus
Family influences on peer relationships were explored in the
Soo Hyun Rhee1,2, John K. Hewitt2, Susan E.
Young2, Robin P. Corley2, Thomas J. Crowley3,
Michael C. Neale4, and Michael C. Stallings2. The etiology of comorbidity in substance
dependence in adolescents.5
1Department of Psychology, University of Colorado, Boulder, CO 80309,
2Institute for Behavioral Genetics, University of Colorado, Boulder,
CO 80309, 3Department of
Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, 4Virginia Institute for
Psychiatric and Behavioral Genetics, Richmond, VA 23298-0126, 5Supported by NIDA
grants DA-05131, DA-11015, and DA-13956.
Address: Institute for
Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309 Telephone: (303) 492-4631 Fax: (303)
492-8063 E-mail: Soo.Rhee@colorado.edu
Knowledge regarding the causes of comorbidity among substance use disorders
can have significant impact on future research examining the etiology of these
disorders. Unfortunately, the
conclusions of past studies examining the comorbidity among substance use
disorders are conflicting, with some studies emphasizing the importance of
common familial influences and others emphasizing the importance of substance-specific
familial influences. Discrepancies in
results may reflect different analytical approaches or differences in the
samples examined. Here, we address the
particular question of the causes of comorbidity in substance dependence in
adolescents. We will examine the causes
of comorbidity in substance dependence in a clinical sample of adolescents
treated for antisocial substance problems and a control sample. The Neale and Kendler model fitting approach will be used to test 13
alternative hypotheses for the causes of comorbidity.
1Department of Psychological Medicine,
Address: Department of
Psychological Medicine, University of Wales College of Medicine,
Depression and anxiety co-occur more commonly than would be expected
by chance in children and adolescents.
This comorbidity has been reported in clinical samples and with
sub-clinical symptoms in the general population (Brady & Kendall, 1992, Psychol Bull., 111, 244-55; Kovacs &
Devlin, 1998, J Child Psychol
Psychiatry.,39,
47-63). The association between anxiety and depression is of interest as
results from family studies have suggested that anxiety may be a genetic
precursor of depression (Rende, Warner, Wickramaratne & Weissman,
1999, Psychol Med., 29, 1291-298). This is thought to
be the case particularly in children at high risk of depression, however family
studies are unable to disentangle genetic and shared environmental
effects. The genetic and environmental
architecture underlying the association between early anxiety and later
depression can be assessed using a longitudinal twin design. All families of
twin pairs born between 1980 and 1991 were identified from a sub-sample of
CASTANET (Cardiff Study of All Wales and Northwest England Twins), a population-based
Frances J. Rice1,2, Gordon T. Harold2, and Anita Thapar1. Negative life events as an
account of age-related differences in the genetic aetiology of depression in
childhood and adolescence.
1Department of Psychological Medicine,
Address: Department of
Psychological Medicine, University of Wales College of Medicine, Heath Park,
Cardiff, CF14 4XN Phone: 044 (0)29 20743241 Fax: 044 (0)29 20747839 Email:
Many twin studies have reported that the genetic aetiology of
depression differs according to age, with genetic influences being more
important for adolescents than younger children. We sought to examine whether this age related
increase in the relative importance of genetic factors is due to an increase in
gene-environment correlation specifically involving negative life events.
Questionnaires were sent to the families of CASTANET (Cardiff
Study of All Wales and Northwest England Twins), a population-based
Frances J. Rice1,2, Gordon T. Harold2, and Anita Thapar1. The transmission of depressive symptoms from
mother to child: genetic and environmental pathways.
1Department of Psychological Medicine,
Address: Department of
Psychological Medicine, University of Wales College of Medicine, Heath Park,
Cardiff, CF14 4XN Phone: 044 (0)29 20743241 Fax: 044 (0)29 20747839 Email:
Although family studies have shown that maternal depression is
associated with depression in children, it is uncertain to what extent this
resemblance is due to genetic factors and how much is
explained by environmental adversity. The relative importance of genetic
and environmental factors in the transmission of depression from mother to
child was evaluated in the CASTANET (Cardiff Study of All Wales and Northwest
England Twins)
Nathan K. Risk1,
Ashley H. Hayden1, Krista L. Russel1, and Rumi K. Price1. The interaction of ALDH@
and CYP2A6 with acculturation on alcohol and nicotine use and problem use among
Vietnamese and Japanese: Preliminary
results from a pilot study.2
1Department of Psychiatry,
Address: Department of
Psychiatry,
In the genetic literature, mutations of two metabolic genes, aldehyde dehydrogenase class 2
(ALDH@) and cytochrome P450 2A6 (CYP2A6), have been
found to be protective against alcoholism and regular cigarette smoking
uniquely among subgroups of Asian population.
However, population epidemiologic data often show findings inconsistent
with this notion of uniform genetic protection among Asians. The widely different rates among Asian
subgroups are partially due to the size of mixed-race subgroups, among whom a
fourfold increase in alcohol and nicotine use is observed. Using pilot data for a larger genetic
epidemiological project, we examine the relative strengths of the two candidate
genes and sociocutural and psychiatric factors
pertaining to alcohol and nicotine use and problem use in the Vietnamese and
Japanese populations. Genotype data on
ALDH2 and CYP2A6 and self-report measures of ethnicity, substance use and
problem use, acculturation, socioeconomic achievement, mental health, and
deviance will be obtained from approximately 160 Vietnamese and 80 Japanese
participants recruited through ethnic-specific community-based organizations
and service providers in St. Louis City and County, Missouri. We report on preliminary results
gathered to date: 1)genotypic distributions of mixed-heritage
vs. unmixed Japanese and Vietnamese; 2)correlations of genotypes of the two
candidate genes with self-reported measures of alcohol use and cigarette
smoking; and 3)differences in genotypes and acculturation measures between the
Japanese and Vietnamese in
Joseph Lee Rodgers. Reformulating and Simplifying the DF Analysis
Model.
Department of
Psychology,
DeFries-Fulker (DF) Analysis for unselected populations is
reformulated as a no-intercept model with centered variables and only two
independent variables. The reformulation
serves three purposes. First, the
original formulation implicitly estimated two different values for c2 and two
values for h2. The new formulation
resolves this ambiguity. Second, because
the original formulation estimated h2 with the coefficient from a regression-interaction
term, whether to center the interaction variables was unclear. The new formulation explicitly resolves this
issue. Finally, the new formulation
estimates fewer parameters, and therefore improves estimation efficiency and
statistical power.
Pierre L. Roubertoux1,2, Brice Marcet3, Franz Sluyter1,4,
and Bernard Verrier3.
Mitochondrial DNA (mtDNA) and behavior :
interaction between mitochondrial and nuclear genes, preliminary results from
micro arrays.
1CNRS Génétique
Address: INPC CNRS 31 rue Chemin Joseph Aiguier, 13402
Marseille France Phone: 33 (0) 491164565 E-mail: rouber@lnf.cnrs-mrs.fr
Nuclear and mitochondrial (mt) genomes
interact. The expression of nuclear genes is modified by mt
genes and mt gene expression may be modified by
nuclear genes as recently reported. New or aggravated phenotypes can result
from these interactions. We investigated the modifications of expression of
nuclear genes, in the brain, after cross transfer of mtDNA in mice. For this
purpose, we used congenic strains for mtDNA (see Carlier et al. and Sluyter et al.
abstracts, same issue). The congenics were derived
from NZB/BlN and CBA/H mice that carry mtDNA from
different origins. We show that mitochondrial genes of complexes I and IV were
polymorphic in NZB/BLNJ and CBA/H. The NZB/BlN mice
were compared to NZB/BlN with mtDNA from CBA/H origin
and CBA/H with CBA/H with mtDNA from NZB/BlN origin.
We used Pan mouse DNA chips covering 30,000 genes,
corresponding to the whole mouse genome (MWG SA, Biotech,
Angelica Ronald1,
Francesca G.
1Social Genetic and Developmental Psychiatry Research Centre,
Address: SGDP Research
Centre Box PO83 Institute of Psychiatry Denmark Hill
SE5 8AF
We investigated the genetic relationship between the two major
components of symptoms in the population that at the extreme characterise autism spectrum disorders: social features
(social and conversational abilities, theory of mind skills) and nonsocial
features (rigidity and stereotyped behaviours,
central coherence). Parents and teachers
of over 3,000 7-year old twin pairs completed a booklet that included three
questionnaires: a questionnaire based on DSM IV social and non-social criteria
for Autistic disorder and Aspergers, the Strengths
and Difficulties Questionnaire (R. Goodman, 1997, J Child Psychol Psychiatry, 38, 581-586),
and a questionnaire on theory of mind in everyday life (U. Frith,
F. Happé, and F. Siddons,
1994, Soc Dev, 3, 108-124). Social and non-social symptom scales showed substantial
heritability (54%-71%) and nonsignificant shared
environmental influence, for both teacher and parent data and for both males
and females. One scale, parent reported
social features, showed modest shared environmental influence (23%). Similar results were found for the entire
sample and for high-scoring extreme groups.
For both the entire sample and the high-scoring extreme groups, the
social and non-social components were only modestly correlated phenotypically. Bivariate genetic analysis indicated that the social and
non-social components of autistic spectrum symptoms are largely influenced by independent
genetic factors. These findings suggest
that there is genetic heterogeneity for social and non-social symptoms of the
autism spectrum, which has implications for diagnosis and treatment of autism
spectrum disorders. For molecular
genetic research, these findings suggest the social and non-social components
of the autism spectrum should be studied separately rather than combined in a
single syndrome.
Alan R. Sanders1
and Pablo V. Gejman1. Human G protein-coupled receptors coding
variation database.2
1Department of Psychiatry,
Address:
G protein-coupled receptors (GPCRs) play
fundamental roles in regulating the activity of almost every cell, typically
functioning to relay a signal from outside to within the cell, and are
especially important for all fields of medicine because they are targets for
most medications. I propose to create a
comprehensive and multipurpose database for human GPCR genes including information
about naturally occurring genetic variations, and use this database to test a
set of hypotheses of fundamental biological significance regarding the general
characteristics of these genetic variations. We will test hypotheses about the position at
which naturally occurring mutations occur in the messenger RNA (mRNA) and the
protein, the type of amino acid affected, induced alterations in the codon usage pattern, and their effect on computer modeled
mRNA
structure. The proposed database
will be integrated into the existing GPCR Database and will provide information
that will facilitate the testing of pathophysiological
hypotheses with positional or etiological candidate genes (that are GPCRs) for major psychiatric disorders by the scientific community. This avenue of research could have
far-reaching implications for human health because of the insight gained by
exploiting this knowledge (e.g., rational drug design) in pursuit of better
understanding variation among genes relevant to most major mental disorders,
such as schizophrenia and mood disorders, or their treatments.
Kimberly J. Saudino1,2. Sex and the Single Teacher.
Sex Differences in Parent- and Teacher-rated Behavior Problems.3
Address:
MA 02215 Telephone: 617 353 3679 Fax: 617 353 6933 E-mail: ksaudino@bu.edu
Although sex differences in mean levels of behavior problems in
childhood have been well-studied, the question of sex differences in the
etiology of behavior problems has been relatively unexamined. The present study explores whether genetic
and environmental influences on parent- and teacher-rated problem behaviors
differ for males and females in a sample of
1857 twin pairs (621 MZM, 725 MZF, 568 DZM, 641 DZF, and 1159 DZO;
mean age 7.04 years) participating in the Twins Early Development Study
(TEDS). Parents and teachers rated the
behavior problems of twins on the Strengths
and Difficulty Questionnaire (SDQ).
Preliminary analyses indicated that there were significant differences
in parameter estimates
for twins in which both members of a pair were rated by the same
teacher versus twins who were both rated by different teachers. Therefore, separate genetic sex-limitation
models were fit to data for parents, same teacher, and different teachers. There was no evidence of genetic sex-differences
when twins' behavior problems were evaluated by parents or different
teachers. However, when both members of
a twin pair were rated by the same teacher, qualitative sex-specific genetic
effects were indicated for hyperactivity.
Similarly, quantitative genetic effects were indicated for prosocial behavior, peer problems and conduct
problems. For these three SDQ scales
males displayed significantly higher heritabilities
than females (prosocial behavior: Males h2
= .76, Females h2 =.51; peer problems: Males h2 = .83,
Females h2 =.60; conduct problems:
Males h2 = .81, Females h2 =.57). These findings suggest ratings of twins'
behavior problems by the same teacher reveals subtle behavioral differences
that can go undetected with parent or different teacher ratings.
Stephanie Schmitz1. Attention and internalizing
problems.2
1Institute for Bahavioral Genetics,
University of Colorado, CO 80309, 2Supported by NIH grants MH-43099,
HD-10333, and MH-62116.
Address: Institute for Bahavioral Genetics, Campus Box 447, University of Colorado,
CO 80309; Telephone: (303) 492-0835; Fax: (303) 492-8063; email: schmitzs@colorado.edu
Most of the literature on problem behaviors co-occurring with attention
problems has been on those from the externalizing domain. In recent years, however, research has also
examined the joint observation of attention and internalizing behaviors, such
as mania (Biederman et al., 1996) and depression (Biederman, Newcorn, \& Spric, 1991). The
current study combines two genetically informative data sets, namely a twin and
an adoption study, both longitudinal and ongoing, to explore the genetic and
environmental associations between attention and internalizing problem
behaviors. Ratings from both the children's mothers and teachers are utilized
at ages 7 and 12, spanning the grade school years. The etiologies of mother- and teacher-rated behaviors, and their associations in particular, are different
in that mother-rated behaviors point towards common genetic and shared
environmental influences while teacher ratings reveal common non-shared environmental
factors.
Jane E. Schreiber1,
Carol A. Van Hulle1, Penny L. Biersach
Clark1, Kathryn Lemery2, and H. Hill Goldsmith1. Genetic and Environmental
Influence on Afternoon and Evening Cortisol Levels.3
1Department of Psychology, University of Wisconsin, Madison, WI, 2Department
of Psychology, Arizona State University, Tempe, AZ, 3Supported by
NIMH Grant R01-MH59785
Address:
Phone: 608 265-2674 Email: jeschreiber@students.wisc.edu
Basal cortisol activity typically
follows a circadian rhythm, peaking in the morning and dropping throughout the
day. At any given time, cortisol level is potentially
affected by three processes (a waking effect, a circadian effect, and a
stress-reactive effect), which vary in their influences. Genetic and
environmental influences on basal cortisol activity
apparently vary throughout the day with morning cortisol
showing the highest heritability (Wust et. al., 2000,
Psychoneuroendocrinology,
25, 707-720). Unpublished data from another of our studies also support a
higher heritability for morning values in children. Research is needed to
address influences on basal activity later in the day. This study estimates
genetic and environmental influences on afternoon and evening cortisol. Participants
were 54 families (20 MZ, 34 DZ, age 6-9 years) participating in the Wisconsin
Twin Project, an ongoing longitudinal study of children at risk for behavior
problems. By June, 2003, the sample size should increase to approximately 200
families. Salivary cortisol samples were collected at
home in the late afternoon and before bedtime over three days, from parents and
twins. Cortisol values were averaged across days. Using a scalar model that assumed the same
factors influenced parents and twins, we found that shared environment
accounted for 40% of the variance in twin evening levels; 49% of the variance
was to due to non-shared environmental effects, and 10% was due to genetic
factors. In general, variance of parental values was not different from the
twin values. Similar results were found for the afternoon sample. With the
enlarged sample, we shall test for cultural and genetic transmission and
analyze the change between time points. This report should help disentangle the
factors of time of day, source of cortisol (blood,
saliva, urine), age of participants, and basal versus
reactive cortisol measures that complicate the
current literature.
Jane Scourfield,
Frances Rice, Anita Thapar, Gordon T. Harold, Neilson
Martin, Peter McGuffin. Depressive symptoms in children and
adolescents: changing aetiological influences with development.
University of
Address: Department of
Psychological Medicine (4th floor), University of Wales College of Medicine,
Parent and self-report questionnaire data was used to examine the
genetic and environmental influences on depressive symptoms in a
depressive symptoms as children grow into adolescence.
Nancy L. Segal1,
William D. Marelich2, Rick Castillo2, Jack Mearns2,
and Shirley A. McGuire2. Problem Behaviors in Virtual Twins: Analysis
of Shared Family Influences.3
Address:
Phone: 714-278-2142, Fax: 714-278-4843, Email: nsegal@fullerton.edu
Behavioral-genetic studies of children’s problem behaviors have
compared behavioral problem scores for monozygotic (MZ) and dizygotic
(DZ) twins and adoptive siblings. Both genetic and environmental factors have
been shown to influence individual differences across scales. The present study
uses a unique kinship called virtual twins (VTs); VTs are same-age, unrelated children raised together,
composed of two adoptees or one biological child and
one adoptee. VTs, therefore, replicate twins’ rearing
situation, but without the genetic link.They
circumvent problematic features of ordinary adoption designs, such as
children’s different age at family entry and different age at testing. The
present analysis was conducted as part of the ongoing Virtual Twins Study at
age was 5.51 years (sd = 2.23) and ranged
between 4 - 16 years. Pairs included 106 males and 94 females. An earlier study
of 40 pairs (1997) found that, with a few exceptions, VT means were generally
comparable to those from a non-referred sample of children 4 - 11 years of age,
as reported in the CBCL manual. In that analysis, VT intraclass
correlations (-.11 to .58 for problem
behaviors and .28, .40 and .51, respectively, for internalizing, externalizing
and total problem scores) were
significantly lower than those of MZ twins, and generally lower than those of
DZ twins, suggesting both genetic and environmental influences. In the present
study, with only a few exceptions, VTs’ mean scale
scores were generally comparable to those of the non-referred sample. VT intraclass correlations ranged between -.02 and .50 for problem
behaviors and were .35, .54 and .74, respectively, for internalizing,
externalizing and total problem scores. Correlations for all scales (except
thought problems) were significantly below those of MZ twins, suggesting
genetic effects. In contrast, VT-DZ twin correlations did not differ. The VTs younger age may be partly responsible, given that
within-family influences are more potent among younger children. Resemblance
between biological-adoptive and adoptive-adoptive pairs will also be presented.
Wendy S. Slutske1,
Andrew C. Heath2, Nikole J. Cronk1,
Kathleen K. Bucholz2, Pamela A.F. Madden2, and Nicholas
G. Martin3. Familial transmission of alcoholism and antisociality: A study of twins and their adult offspring.4
1Department of Psychology and Missouri Alcoholism Research Center,
University of Missouri, Columbia, MO 65211, 2Department of
Psychiatry and Missouri Alcoholism Research Center, Washington University
School of Medicine, St. Louis, MO, 63110, 3Epidemiology Unit,
Queensland Institute of Medical Research, Brisbane, Queensland, Australia, 4Supported
by NIH grants AA00264, AA07535, AA07728, and AA11998.
Address: Department of
Psychology, University of
Although it has been widely embraced by the treatment community,
and certainly has a great deal of intuitive appeal, it has been difficult to demonstrate
empirically a (non-genetic) consequence of being reared by an alcoholic parent.
In particular, twin studies have generally led to the conclusion that family
environmental influences do not play a major role in the familial transmission
of alcoholism risk. However, in the twin
design the estimate of family environmental effects only includes those that
are independent of genetic effects. One critical test for demonstrating an
important environmental effect of being reared by an alcoholic parent is to
compare the rates of adverse outcomes among the biological offspring of
alcoholic parents to the rates of adverse outcomes among the biological
offspring of the unaffected cotwins of alcoholic parents.
In this paper, we examine the history of alcohol use disorders and conduct
disorder among 774 offspring of 408 parents from same-sex twin pairs who were
characterized by the history of alcohol use disorder and conduct disorder in
themselves and their cotwin. For example, of the 408 parents, 127 had a
personal history of alcohol dependence, 28 were unaffected but had a
monozygotic cotwin with a history of alcohol dependence,
33 were
unaffected but had a dizygotic cotwin
with a history of alcohol dependence, and 220 were unaffected with an
unaffected cotwin.
Offspring of parents from these four groups were at varying degrees of genetic
(high, high, intermediate, and low, respectively) and environmental (high, low,
low, and low, respectively) risk for alcohol dependence. Preliminary analyses of these data suggest
that the only group of offspring who had significantly elevated rates of
alcohol dependence and conduct disorder (compared to the low risk group) were those
with both high genetic and high environmental risk.
Frans Sluyter1,2, Charles Cohen-Salmon1,3, Michèle Carlier1,4, Chabane
Chérif1, Fatima Maarouf Verray1,
and Pierre L. Roubertoux1,5.
Mitochondrial DNA and behavior: Implication of mitochondrial DNA in
learning and memory.
1CNRS Génétique Neurogénétique
Comportement, France, 2Present address:
SGDP Centre, Institute of Psychiatry, London, UK, 3UMR 7593 CNRS and
Université Paris VI, Paris, France, 4Present
address: PsyCLÉ (EA3273), Université
de Provence, France, 5Present address:
INPC CNRS 31, Marseille, France. Supported
by the CNRS to Génétique Neurogénétique
Comportement and to Institut
des Neurosciences Physiologiques et
Cognitives. F. Sluyter
received a fellowship from the Fondation Fysen and Cohen Salmon a financial support from Laboratoire Ipsen.
Address: SGDP Centre,
Phone: Tel: 44-(0)207-848-0028 Fax: 44-(0)207-848-0866 Email: F.Sluyter@iop.kcl.ac.uk
Although the role of mitochondrial DNA (mtDNA) in normal and abnormal
development of the nervous sytem has been well
established, only one study so far has hinted at an association between mtDNA
and cognition. Using a congenic quartet of
well-selected inbred strains (NZB/BlN and CBA/H male
mice, see (Carlier et al. abstract), we here provide
direct evidence for the
implication of mtDNA in learning and memory. We measured the congenic quartet's performance in three distinct
behavioral paradigms (Morris water maze,
8-arm radial maze & Krushinsky task), all of
which have been validated to reflect
'mouse cognition' and all of which tap into different combinations of reward mechanisms and locomotor demands. mtDNA effects mostly
occurred in interaction with nuclear DNA and persisted with age, increasing in
magnitude as the mice got older. In addition to other mtDNA effects on
exploration, sensorial development and brain anatomy, the present findings clearly show that
mitochondrial polymorphisms are not as neutral as was previously believed and
might, at least partly, explain the sometimes enigmatic observations in mammals
generated by cloning and assisted reproduction.
Frans Sluyter1 and Leonard C Schalkwyk1. Symposium: Using microarrays
in the analysis of behavior.
1Social, Genetic and Developmental Psychiatry Research Centre,
Address: Social, Genetic
and Developmental Psychiatry Research Centre, PO 82, Institute of Psychiatry,
King's College London, De Crespigny Park, London SE5
8AF, U.K. tel: +44(0)207 848 0028 fax: +44(0)207 848
0801 email spjgfns@iop.kcl.ac.uk
Microarray methods are becoming increasingly widely used in many kinds of
genetics and are even beginning to penetrate into the study of behavior. One
application is high throughput SNP genotyping.
Other applications allow the function of genes to be explored. As technological advances allow ever more
ingenious applications to be dreamed up, the prospects are good for a
chip-dominated decade. This symposium
combines three highly novel uses of microarrays in
mouse behavioral genomics and one leading application of microarrays
to human behavioral genetics.
Erica L. Spotts1
and Paul Lichtenstein1. Early adolescent behavior problems and middle
adolescent relationships: Genetic and
environmental influences.2
1Karolinska Institutet, Department of
Medical Epidemiology, Stockholm, Sweden, 2The Young Twins project is
supported by the Swedish Council for Working Life and Social Research (project
2001-2368) and the Swedish Research Council (2001-4231). The first author is supported by NRSA grant
MH65008.
Address: Karolinska Institutet, Department
of Medical Epidemiology,
Research on adult relationships has found that mental health and
adjustment are important associates of relationship quality (ie. Beach, S.R., Fincham,
F.D. & Katz, J., 1998, Clinical
Psychology Review, 18, 635-661.).
Relationships become increasingly
important in adolescence so we wanted to see if earlier adjustment was a
predictor of later relationship quality.
The few studies that have examined this association in adolescence have
found associations between internalizing and externalizing behaviors and friend
relationships (Klein, D.N., Lewinsohn, P.M, &
Seeley, J.R., 1997, Journal of Affective
Disorders, 42, 2-3), sibling relationships (Deater-Deckard,
K., Dunn, J. & Lussier, G., 2002, Social Development, 11, 571-590; Dunn,
J., Slomkowski, C., Beardsall,
L & Rende, R., 1994, Journal of Child Psychology & Psychiatry & Allied Disciplines, 35,
491-504), and romantic relationships (Grello, C.M,
Dickson, J.W., Welsh, D.P., et al, 2001, paper presented at Society for
Research on Child Development conference,
Minneapolis, MN). The current
study will examine the genetic and environmental influences on associations
between early adolescent internalizing and externalizing behaviors and
mid-adolescent sibling, friend, and romantic relationships. Data from three waves of the Swedish Young
Twins study will be used. Twins were 8-9
years at time 2, 13-14 years at time 2, and 16-17 years at time 3. Behavior problems were assessed at Times 1
(parent reports) and 2 (parent, self, teacher reports), and the quality of
sibling, friend and romantic relationships (self reports) was assessed at Time
3. Analyses show that externalizing, but
not internalizing, at Time 2 is associated with sibling relationships and some
aspects of friend and romantic relationships at Time 3. Genetic influences seem to account for most
of the associations between externalizing and relationships, though these
influences may differ by gender.
Findings suggest that the quality of adolescent relationships may
originate in genetically influenced aspects of earlier adjustment.
Michael C. Stallings1,
Robin P. Corley1, Brianna Dennehey2, John K. Hewitt1,
Kenneth S.
Krauter2,
Jeff M. Lessem1, Susan K. Mikulich3, Soo
Hyun Rhee1, Andrew Smolen1, Susan E. Young1,
and Thomas J. Crowley3. A Genome Scan for Quantitative Trait Loci
Influencing Antisocial Drug Dependence in Adolosence.4
1Institute for Behavioral Genetics, University of Colorado,
Boulder, CO 80309, 2Department of Molecular, Cellular and
Developmental Biology, University of Colorado, Boulder, CO 80309, 3Division
of Substance Dependence, University of Colorado School of Medicine, Denver, CO
80262, 4Supported in part by NIH Grants DA-05131, DA-11015, and
DA-12845
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
There is substantial comorbidity among substance use disorders and
externalizing problem behavior, particularly in adolescence. Increasing
evidence suggests that familial influences, including shared genetic risk
factors, may account for part of this comorbidity. In this study we describe
results from a genome-wide search for quantitative trait loci (QTL) influencing
substance dependence vulnerability and externalizing problem behavior in adolescence. The gene mapping goals of the Center on
Antisocial Drug Dependence at the
Anita Thapar1,
Tom Fowler1, Frances Rice1, Jane Scourfield1,
Marianne van den Bree1, Hollie Thomas1,
Gordon Harold2, and Dale Hay2. Maternal
smoking in pregnancy and Attention Deficit Hyperactivity Disorder symptoms in
offspring.
1Department of Psychological Medicine, University of Wales College
of Medicine, Cardiff, UK, 2School of Psychology, Cardiff University,
Cardiff, UK
Address: Professor Anita Thapar, Professor of Child and Adolescent Psychiatry, Department
of Psychological Medicine, University of Wales College of Medicine, Heath Park,
Cardiff CF14 4XN, UK Phone: 044 (0) 29 2074 3241, Fax: 044 (0) 29 2074 7839,
Email: thapar@cardiff.ac.uk
Maternal smoking in pregnancy has been found to be associated with
Attention Deficit Hyperactivity Disorder (ADHD) in several clinical studies.
Confounding factors do not appear to account for the association. However, with
the exception of one study, this work has been based on clinical samples.
Population-based studies have focused on the association with Conduct Disorder
symptoms. The aim of the study was examine whether smoking in pregnancy is
associated with ADHD symptoms in offspring and that these effects are
additional to genetic influences, using a population-based twin sample.
Children's ADHD symptoms (parent and teacher rated), maternal smoking in
pregnancy, conduct disorder symptoms and family adversity were assessed using
questionnaires in a population-based sample of 1,452 twin pairs aged 5 to 16
years from the CAST-A-NET sample (Cardiff Study of All Wales and North West
England Twins). Although genetic influences accounted for most of the variants
in offspring ADHD, smoking in pregnancy was still found to show a significant
environmentally mediated association. Maternal smoking remained a significant
influence when other potential confounders were taken into account. In
conclusion, maternal smoking in pregnancy appears to show an association with
ADHD symptoms in offspring that is additional to the effects of genes and not
attributable to shared rater effects, clinical referral biases or co-variation
with antisocial behaviour.
Anita Thapar, Kate Langley, Lucy Marshall, Marianne van den Bree, Hollie Thomas, Michael
Owen, and Michael O'Donovan. ADHD children with and without the dopamine
D4 receptor 7-repeat allele: evidence of differences in performance on
neuropsychological tests.1
Department of Psychological Medicine,
Address: Professor Anita Thapar, Professor of Child and Adolescent Psychiatry, Department
of Psychological Medicine, University of Wales College of Medicine, Heath Park,
Cardiff CF14 4XN, UK Phone: 044 (0) 29 2074 3241, Fax: 044 (0) 29 2074 7839,
Email: thapar@cardiff.ac.uk
Association between the 7-repeat allele of a variant in the DRD4
gene (a 48bp VNTR) and ADHD has been widely documented with evidence of
significant association from a meta-analysis of 21 studies (Faraone,
SV, Doyle AE, Mick E and Biederman J, American Journal of Psychiatry, 2001, 158:7,1052-1057).(1) We examine whether the DRD4 7-repeat allele
is associated with performance on a variety of neuropsychological tasks. 133
drug-naive children aged 6 to 13 years who fulfilled diagnostic criteria for
ADHD were assessed on several neuropsychological tests (continuous performance
test, matching familiar figures test (MFFT), go-no-go task and stop task). Activity level was assessed with an Actigraph. Those with at least one 7-repeat allele
(7-present) and those without (7-absent) were compared. We also compared
results from the clinical sample with existing comparison data. Compared to the
7-absent group, the 7-present group showed a significantly increased number of
incorrect responses on the MFFT (16.1 vs. 14.3, p=0.001), decreased mean
reaction times for incorrect responses on the MFFT (846.1ms vs. 1103.7ms,
p=0.02) and on the Stop task (116.6 vs. 134.1ms p=0.029). The 7-present group also displayed increased
activity levels assessed using an actigraph
(t=-2.115, p=0. 037). No significant differences were found on measures of sustained
attention or percentage of inhibitions. Both ADHD groups were more impaired
than comparisons. In conclusion children with ADHD, possession of the DRD4
-7-repeat allele appears to be associated with an inaccurate, impulsive
response style on neuropsychological tasks that is not explained by ADHD
symptom severity.
Anita Thapar1,
Jacky Boivin2, Gordon Harold2, Dale Hay2,
1Department of Psychological Medicine, University of Wales College
of Medicine, Cardiff, UK, 2School of Psychology, Cardiff University,
Cardiff, UK, 3Supported by Wellcome Trust
Showcase Grant 067527/Z/02/Z
Address: Professor Anita Thapar, Professor of Child and Adolescent Psychiatry, Department
of Psychological Medicine, University of Wales College of Medicine, Heath Park,
Cardiff CF14 4XN, UK Phone: 044 (0) 29 2074 3241, Fax: 044 (0) 29 2074 7839,
Email: thapar@cardiff.ac.uk
It is undisputed that genes and environmental factors affect
health and behaviour. Even after specific genes are identified, methods for
understanding how they work together with environmental factors will still be
needed. Family, twin and adoption studies are widely used genetic
epidemiological methods. We propose a new strategy based on families using in
vitro fertilisation (IVF). Children conceived via
these methods may be genetically related to both parents
(homologous IVF), the mother only (sperm donation), the father only (egg
donation) or to neither parent (surrogacy). In all cases the social mother
experiences the pregnancy. With surrogacy both parents are genetically related
to their child but the child is born to a genetically unrelated surrogate. By
comparing the similarity of parent and offspring across each of these groups we
can examine not only the contribution of genes but also disentangle the effects
of genes, intrauterine and early environmental influences. It will also be possible
to examine to what extent the association of specific environmental risk
factors and behaviour is mediated by genes and environment. The main aims of
the study will be to (1) test the separate and joint influences of genes,
intrauterine and environmental effects on a variety of behaviours
(2) explore the feasibility of this method to be used more widely.
Laura M. Thornton1,
Martin E. Hahn2, and Norman Schanz2. Genetic
and Developmental Influences on Infant Mouse Ultrasonic Calling. III.
Patterns of Inheritance of Call Characteristics.3
1Eating Disorders Research, University of Pittsburgh Medical
College,
Infant mice produce ultrasonic calls that elicit retrieval by
adult mice. Age-related differences in
some of the call characteristics have been noted (M. E. Hahn, L. Karkowski, L Weinrub, A. Henry,
Alexandre A. Todorov1, Shimy Apoorva2,
and Richard Todd1,3. Sample size as a random variable and its
effect on power computations.4
1Departments of Psychiatry and 3Genetics, Washington
University School of Medicine,
Address: Department of
Psychiatry, 40N Kingshighway Suite 1, St Louis MO
63108 Phone: 314 286 2301 Fax: 314 286 2213 Email: todorov@matlock.wustl.edu
Power computations are an integral part of study design and are
generally done assuming a fixed or "expected" sample size (e.g.,
number of affected sib pairs). Oftentimes, however, the final sample size is
not known in advance. We illustrate here power computations for a linkage study
of ADHD (prevalence between 3 and 5%, sibling relative risk between 3 and 7)
which uses a multistage sampling scheme, and faces three common constraints: (i) sampling from a finite population (here, N=11,502 large
families in Missouri); (ii) budgetary limit on the total number of families
that can be screened; and (iii) budgetary limit on the total number of
individuals that can be genotyped. Thus, neither the exact size nor the final composition of the sample are known in advance. In our
example, we determined that the study would end with 300-400 affected sib-pairs
and that power would be acceptable (taking into account fluctuations in sample
size and composition) to detect a gene accounting for about ~4% of the
liability to ADHD. The methods have been
implemented in a program available from the authors. Six parameters (respondent
cooperation rate, screening test sensitivity and specificity, individual-wise
cooperation rate, diagnostic test specificity and sensitivity) are used to
determine the probability distribution of the numbers of recruited affected and
unaffected sibs, conditional upon the true number of affected and unaffected
individuals in that family. For various genetic models, we then calculate the
frequencies of families with a given number of affected and unaffected
offspring. From these, we determine the probability distribution of family
types types (defined by the number of affected and unaffected offspring that participate) under
the multistage sampling scheme, taking into account practical constraints
(population size, budgetary), and use this distribution to estimate power for
the all-pairs test.
Marianne van den Bree1,
Lucie Robinson1, Darko Turic1,3,
Mary Duke1, Derek W. Morris1, Marian Hamshere1,
Andrew Grierson1, Martha Easton1, Ruma
Raha-Chowdhury2, Jeffery Gruen3, Jim Stevenson4,
Michael Krawczak1,5, Michael J. Owen1, Michael C. O'Donovan1,
Julie Williams1. Linkage
disequilibrium mapping provides further evidence of a gene for reading
disability on chromosome 6p21.3-22.
1Department of Psychological Medicine, University of Wales College
of Medicine, Heath Park, Cardiff, UK, 2Department of Neuroscience
and Cognitive Development, Babraham Institute, Babraham, Cambridge, UK, 3Yale Child Health
Research Center, OA464 Congress Avenue, New haven, USA, 4Centre for
Research into Psychological Development, University of Southampton,
Southampton, UK, 5Department of Medical Genetics, University of
Wales College of Medicine, Heath Park, Cardiff, UK
Address: Department of
Psychological Medicine, University of Wales College of Medicine, 4th Floor,
Heath Park, Cardiff CF5 3PU Phone: 029-20743242 Fax: 029-2074 7839 Email:
Using a two-stage approach, we tested for association between
reading disability (RD) and 22 microsatellite markers
in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/proband trios in which RD was rigorously defined. The most
significant replicated associations were observed between combinations of
markers D6S109/422/1665 (Stage 1, P=0.002 (adjusted for multiple testing);
Stage 2, P=0.0001) and D6S506/1029/1660 (Stage 1, P=0.02 (adjusted), Stage 2,
P=0.0001). The only two-marker association observed in both samples was with D6S422/1665
(P=0.01, 0.04). No single marker showed replicated association but D6S506
produced values of P=0.01 and 0.08 which were significant when combined
(P=0.02). We observed weaker and less consistent evidence of association in a
region of confirmed linkage to RD in previous studies. The most consistently
significant haplotypic association D6S109/422/1665,
showed association with single-word reading, spelling, phonological awareness,
phonological decoding, orthographic accuracy and random automised
naming, but not with vocabulary or Attention Deficit Hyperactivity Disorder.
Our findings strongly support the presence of a gene contributing to RD in a
region of chromosome 6 between markers D6S109 and D6S1260, but do not rule out
the presence of a gene between D6S1556 and MOG.
Edwin
JCG van den Oord1. A framework for controlling discovery rates and minimizing the
amount of genotyping in LD studies.2
1Virginia Institute for Psychiatric and Behavioral
Genetics, Medical College of Virginia of
Address: Virginia Institute
for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical
College of Virginia of
I explore how linkage disequilibrium studies may be designed
efficiently using a sequential design. The method allows researchers to set
false and true discoveries at desired numbers, perform power calculations for
LD studies involving a large number of SNPs, and
compute required sample sizes while minimizing the genotyping burden. The
approach is illustrated for a fine mapping study and a whole-genome scan.
Edwin
JCG van den Oord1. Ethnic differences in birth weight.2
1Virginia Institute for Psychiatric and Behavioral
Genetics, Medical College of Virginia of
Address: Virginia Institute
for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical
College of Virginia of
Ethnic differences in birth weight have remained largely
unexplained. Birth weight is correlated with developmental outcomes and health.
It is therefore important to identify the factors that might put specific
ethnic groups at high risk. However, the large domain of possible influences,
and the difficulty of measuring them in large surveys, makes a resolution of
the causes underlying ethnic differences in birth weight difficult. We
therefore apportioned the ethnic differences in general components by fitting a
quantitative genetic model to data from the National Longitudinal Survey of
Youth and studied biracial infants using the whole 1991 birth cohort as collected
by the U.S. National Center of Health Statistics. Results were very consistent
and provided guidelines how to advance research on ethnic differences in birth
weight.
Richard J. Viken1,
Danielle M. Dick1, Jaakko Kaprio2,
and Richard J. Rose1. Trajectories of Drinking from Adolescence to
Young Adulthood: Genetic and Environmental Effects.3
1Department of Psychology,
Address: Indiana University
Department of Psychology,
In most samples alcohol consumption levels change dramatically during
the period from mid-adolescence to young adulthood. Past research has found equally dramatic
changes in the determinants of drinking, with shared environmental effects
typically decreasing during this period and additive genetic effects
increasing. Although it is possible to
investigate developmental changes in the magnitude of genetic and environmental
effects by cross-sectional studies of twins varying in age, much more
information can be obtained from longitudinal analyses of twins measured
repeatedly across a crucial developmental period. Drinking in the 2500 twin
pairs of the FinnTwin16 study has now been assessed on four occasions: age 16,
age 17, age 18.5, and age 23. These
repeated assessments make it possible to evaluate changes in drinking patterns
and their determinants in a longitudinal framework. We used a variety of analytic techniques to
evaluate genetic and environmental effects on mean levels of drinking as well
as trajectories of developmental change in drinking from age 16 to age 23. Because the twins were assessed on a variety
of personality and other individual differences measures at age 16, we also
evaluated genetic and environmental associations between individual
characteristics at age 16 and both average drinking and patterns of change in
drinking over the next seven years.
Holly C. Wilcox1,2, Jenae Neiderhiser1,
and David Reiss1. Genetic and
Environmental Influence on Adolescent Cannabis Use: The Role of Family
Relationships.3
1Center for Family Research, Department of Psychiatry and Behavioral
Sciences, George Washington University, Washington, DC, 2Department
of Mental Health, Bloomberg School of Public Health, Johns Hopkins University,
Baltimore, MD, 3Supported by NIH grants MH43373, MH48825 and MH19833
Address:
Recent evidence, using genetically informed designs, indicates the
importance of family environment on the use of cannabis, as compared with other
drugs (K.S. Kendler and C.A. Prescott, 1998, Am. J. Psychiatry, 55, 1016-1022; M.T. Tsuang, M.J. Lyons, J.M. Meyer, et al., 1998, Archives of General Psychiatry, 55, 967-972;
M.T. Lynskey, A.C. Heath, E.C. Nelson, et al., 2002, Psychological Medicine, 32,
195-207). The current study will examine
how aspects of parent-child relationships relate to adolescent cannabis use.
Potential familial transmission and specific aspects of parent-child
relationships, such as conflict/negativity and parental monitoring, will be
studied as potential influences on the pathway to adolescent cannabis use. The
relative contribution of genetic, shared and unique environmental influences on
cannabis use and the role of family relationships will be assessed at two
distinct points in adolescent development.
The data for this study is from the first two waves of the Nonshared Environment in Adolescent Development (NEAD)
project, a longitudinal study designed to investigate the role of nonshared environment on adolescent development. The sample
consists of a total of 720 two-parent families across the
Robert. W. Williams1,
Lu Lu1, Yanhua Qu1, Jintao Wang1, Elissa
J. Chesler1, Hui-Chen Hsu1,
John D. Mountz1, David W. Threadgill1, Kenneth F. Manly1. Brain Transcriptional Networks.2
1Center of Genomics and Bioinformatics,
Address: Department of
Anatomy and Neurobiology, University of Tennessee Health Science Center,
Variation in mRNA levels measured using microarrays
is generated primarily by environmental differences and gene variants. This
variation often has important functional and behavioral repercussion. We are
exploiting recombinant inbred (RI) strains in combination with microarrays to map large sets of cis-
and trans-acting modulators of transcriptional activity in mouse brain.
These same strains have been used extensively for behavioral
analysis (see http://webqtl.roswellpark.org/search.html).
Arrays of most RI lines were hybridized
in triplicate with pooled brain samples from females at three ages. Our current
mapping panel consists of 30 BXD strains. We developed custom programs and
procedures to map each of 12422 transcripts using a data set consisting of
approximately 600 microsatellite markers. We have
mapped ~650 cis- and transacting loci that modulate
the expression of key CNS genes such a receptors, ion channels, and transmitter
transporters. Given the large numbers of traits that we have tested,
a sizable fraction of QTLs are false positives. Even
by the most conservative Bonferroni correction, we
have mapped 40 to 50 new transacting QTLs. The prior
probability that expression of a transcript is modulated by a linked QTL (for
example, a promoter variant) is far higher than that of a randomly interval.
Transacting QTLs with LODs
above 5 are likely to be genuine whereas a majority of cis-acting
QTLs with LOD scores above 1.5 to 3.0 are likely to
be correctly identified. The collection of QTLs have
unexpected and intriguing patterns of distribution. For example, an interval on
proximal Chr 9, associated with the RNA helicase gene Ddx25, harbors over ~8% of all significant
loci. This massively parallel approach to mapping QTLs
that control gene expression poses significant statistical challenges but
offers an even more significant opportunities to dissect
transcriptional networks.
Hong Xian1, Jeffrey
Scherrer2, Seth A. Eisen1, and William R. True2. The role
of post-traumatic stress disorder in explaining the association between combat
trauma and lifetime nicotine or alcohol dependence.
1VAMC Research Service and department of Internal Medicine,
Address:
Trauma, including combat, has been shown to be associated with
increased substance use. In particular, previous studies have found increased
intake of nicotine and alcohol following severe trauma. Yet it is not known if
these associations operate through the development of post-traumatic stress disorder
(PTSD) or another mechanism. We investigated, after controlling for the genetic
and environmental contributions to PTSD, whether and to what degree genetic and
environmental contributions overlap between combat and nicotine dependence (ND),
and between combat and alcohol dependence (AD). Subjects were 3,120 monozygotic
and dizygotic male-male twin pair members of the Vietnam
Era Twin (VET) Registry. Separate Cholesky trivariate models were fit to estimate the magnitude of
genetic and environmental contributions to the co-occurrence of combat and ND
and combat and AD after controlling for the genetic and environmental contributions
to PTSD. The liability for combat was due to about 4.0% additive genetic and
10.2% unique environmental contributions common to PTSD and ND, and to PTSD and
AD, respectively. After controlling for PTSD, we found no evidence of genetic
and environmental overlap between combat and ND, or between combat and AD. Additive genetic influences specific to combat accounted for about
29.2% of the total variance in combat. The remaining variance for combat
was due to unique environmental factors specific to combat,
which accounted for about 56.3% of the variance in combat. These
results suggest that the association between combat and ND, and between combat
and AD observed by previous studies, in fact, operate through the mediation of
the development of PTSD.
Susan E. Young1,
Andrew Smolen1, Michael C. Stallings1, Robin P. Corley1,
John K.
Hewitt1. Anxiety and depression from early to late
childhood: A sibling-based
association study of the serotonin transporter polymorphism.2
1Institute for Behavioral Genetics, University of Colorado,
Boulder, CO, 2Supported by the following NIH Grants: MH-01865,
MH-43899, DA-11015, DA-05131, HD-18426; and the John D. and Catherine T. MacArthur Foundation
Address: Institute for
Behavioral Genetics, UCB 447,
Childhood internalizing problems are often precursors in the
development of more serious psychiatric syndromes including anxiety and
depressive disorders. Twin studies of
the etiology of these disorders suggest that the genetic risk factors underlying
anxiety and depression are highly correlated.
We examined the association between childhood internalizing problems and
a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in 711
children participating in a longitudinal twin study of behavioral and emotional
development. Internalizing problems were
measured at ages 4, 7, 9, 10, 11 and 12 years using the Child Behavior Checklist
(CBCL) parent report form, and at age 12 using the Separation Anxiety,
Generalized Anxiety and Major Depressive Disorder modules of the Diagnostic Interview Schedule for Children. We applied a sibling-based methodology for estimating allelic association with quantitative traits, while controlling for population stratification.