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Marc Jamon and Michel Pratte. Neural adhesion cell disorders.
Functional genomics, pathology and behavior CNRS,
Marseille
Plasticité et Physiopathologie de la Motricité, UMR
6196 CNRS / Université de la Méditerranée 31, Chemin Joseph Aiguier 13402
Marseille Cedex 20, France E-mail :
Cell adhesion molecules
(CAM) are transmembrane proteins that play a role in many functions involved
in the development of neural circuitry, including neurite growth and
fasciculation, axon guidance and synaptogenesis. The L1 family of CAM
(L1CAMs) includes L1, CHL1, NrCAM, NgCAM, and neurofascin in vertebrates. The
gene encoding the prototype of the family, L1 (on chromosomeXq28), is the
target for mutations in the human mental retardation syndrome known as CRASH
(acronym for corpus callosum agenesis, retardation, aphasia, spastic
paraplegia, hydrocephalus) or L1 disease. Recently was generated a mutant
mouse with a deletion for the gene coding for another member of the family,
CHL1, the Close Homologue of L1. The deficiency in this molecule might be
expected to produce L1 deficiency-related deficits, due to the homology and
to a wide overlapping expression of the two molecules. In the present study,
the CHL1-deficient mice displayed signs of decreased stress and a modification
of exploratory behaviour. The mice also showed motor impairments on the
Rotarod, but they were able to move as fast as controls in the alleys of a
T-maze. The observed changes were assumed to be related to a deficit in
attention or in novelty processing. The results are discussed in relation
with motor and cognitive deficits in the human, and possibly schizophrenia,
caused by mutations of the distal part of the chromosome 3 which contains
the CHL1 ortholog.
Wendy
Johnson, Matt McGue, and William G. Iacono1. Genetic and
environmental influences on academic achievement trajectories during adolescence2.
1Department
of Psychology, University of Minnesota, Twin Cities, Minneapolis, MN
USA, 2The Minnesota Twin
Family Study is supported by National Institute on Drug Abuse Grant #DA05147
and National Institute on Alcohol Abuse and Alcoholism Grant #AA09367.
Address : Department of Psychology, University of
Minnesota, 75 East River Road, Minneapolis, MN 55455 Telephone: 952-473-1673
Fax: 952-473-1998 Email: john4350@tc.umn.edu
Using the
population-based Minnesota Twin Family Study, we investigated the main and
interactive effects of child ability, motivation, depression, disruptive
behavior, and family social risk at age 11 on academic achievement
trajectories through high school. Hierarchical linear modeling showed main
effects on initial level of achievement for all variables, though ability
mitigated the effects of family risk. Only family risk showed a main effect
on change in achievement over time, tending to impact it negatively. Girls
showed higher overall achievement than boys, and the gap widened over time.
Influences on achievement level were largely genetic (60% in girls, 50% in
boys), and mediated primarily by genetic influences on ability, motivation,
and disruptive behavior. Shared environmental influences on achievement
level (25% in girls, 30% in boys) were mediated similarly. Influences on
change were also largely genetic (60% in girls, 70% in boys) with the major
contribution from genetic influences on family risk. This suggests that
genetic and environmental influences tend to reinforce each other in the
determination of academic trajectories. Interventions intended to improve
academic achievement should reflect this.
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Jaakko Kaprio1, Urho M.
Kujala2 and Richard J Rose3. The development of
health-related behaviors from adolescence to young adulthood - a
longitudinal twin study4.
1 Department
of Public Health, University of Helsinki, Helsinki, Finland and Department of Mental Health and Alcohol
Studies, National Public Health Institute, Helsinki, Finland, 2
Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland, 3
Department of Psychology, Indiana University, Bloomington, Indiana, USA, 4
Supported by the Academy of Finland and AA-12502
Address: Dept. of Public Health,
University of Helsinki, PO Box 41, FIN-00014 Helsinki, Finland,
Telephone: +358 9 191 27 595 Fax: +358 9 191 27 600 Email: jaakko.kaprio@helsinki.fi
Physically active
lifestyle is associated with many positive health habits, while alcohol
abuse and smoking are associated with many negative outcomes. We studied twins to examine which
associations between physical activity, other health habits and outcomes can
be accounted for by childhood family environment or genetic factors. We
studied how persistent physical activity in late adolescence (based on
questionnaire studies at the ages of 16, 17 and 18.5 years in the FinnTwin16
study ) predicted questionnaire-reported health habits and outcomes at the
mean age of 24 years. The final study group of 4240 individuals included
1870 twin pairs. Those who reported in all the three baseline questionnaires
that their frequency of leisure physical activity was more than 3 times a
week were classified as persistent exercisers and those who exercised less
than 3 times a month were called persistently inactive, and others were
occasional exercises. Follow-up outcomes included measures of physical
activity, self-estimated health, daily smoking, use of illicit drugs, use of
alcohol and relative weight. Pairwise analyses were done within pairs,
comparing a physical active twin with the inactive co-twin. In analyses of
both individuals and discordant co-twins persistent physical activity in
adolescence was a significant predictor of high physical activity and very
good self-estimated health at follow-up (p=0.003). Persistent physical
inactivity compared to persistent activity predicted increased risk of daily
smoking (p<0.001 for individual based analyses and p=0.017 for pairwise
analyses) as well as increased risk of using drugs (p<0.001 and p=0.007,
respectively). The associations between baseline physical activity and
follow-up indices of overweight or use of alcohol were not found to be
statistically significant in pairwise analyses. Persistent physical activity
at late adolescence appears to be causally related to adult physical
activity, self-estimated health, low smoking and low illicit drug use.
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Ariel Knafo1,
Alessandra C. Iervolino1 and Robert Plomin1.
Masculine Girls and Feminine Boys: Genetic and Environmental Contributions
to Atypical Gender Development in Early Childhood2.
1Social,
Genetic and Developmental Psychiatry Research Centre, Institute of
Psychiatry, King=s College
London, United Kingdom, 2Supported by a program grant (G9424799)
from the UK Medical Research Council programme.
Address : Social, Genetic, and Developmental
Psychiatry Research Centre, Box PO80, Institute of Psychiatry, De Crespigny
Park, London SE5 8AF, UK. Telephone: +44 (0) 20 7848 0963. Fax: +44 (0) 20
7848 0895. E-mail: arknafo@hotmail.com.
In this first prospective genetic study of atypical gender role
development, parents of 5799 same-sex pairs of twins from the Twins= Early Development Study (TEDS) reported
on their twin children=s level of
masculinity and femininity at 3 and 4 years. Boys were selected as
gender-atypical if they were highly feminine (top 5%, 10%, or 15%) relative
to other boys. Girls were selected as gender-atypical if they were highly
masculine relative to other girls. Gender-atypical boys and girls were each
divided into two groups: fully gender-atypical children (e.g., feminine boys
also low on masculinity) and partially gender-atypical children (e.g.,
feminine boys who are not low on masculinity). DF extremes analysis yielded
moderate group heritability and substantial shared environment effects for
atypical gender role behavior at 5%, 10% and 15% cut-offs. However, for
fully gender-atypical girls, group heritability accounted for most of the
variance, and shared environment had no effect. The results are discussed in
light of past studies and potential implications for atypical gender
development.
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Karestan C. Koenen1,2,3.
Sex differences in the relationship between IQ and antisocial behavior in
young children.
1Boston
University School of Medicine, 2Boston University School of
Public Health, 3National Center for PTSD, VA Boston Healthcare
System. Supported by NIH GRANT 1K08MH70627
Address :
Women=s Health Sciences Division (116B-3),
National Center for PTSD, VA Boston Healthcare System, 150 South Huntington
Street, Boston MA 02139
Telephone: 617 232
9500 x5913 Fax: 617 278 4515 Email: Karestan.Koenen@bmc.org
Early onset
antisocial behavior is a strong risk factor for poor mental health,
criminality, unemployment, and a host of other adjustment problems in adult
life ( T.E. Moffitt, A. Caspi, H. Harrington, and B.J. Milne, 2002, Development
& Psychopathology, 14, 179-207).
Understanding the etiology of antisocial behavior in young children
is necessary to inform prevention efforts, and therefore, remains an
important public health goal. Low IQ
is a consistent risk factor for antisocial behavior across the life course (
J.T. Nigg and C.L. Huang-Pollock, 2003, in B.B. Lahey, T.E. Moffitt, and A.
Caspi, eds., Causes of Conduct Disorder and Juvenile Delinquency,
Guilford: New York). Antisocial
behavior in childhood is also more prevalent among males then females and
evidence suggests compromised intelligence has greater effects on the
development of antisocial behavior in males (T.E. Moffitt, A. Caspi, M.
Rutter, and P.A. Silva, 2001, Sex differences in antisocial behavior:
conduct disorder, delinquency, and violence in the Dunedin Longitudinal
Study, Cambridge University Press: Cambridge, UK). This paper uses data from the Environmental
Risk (E-Risk) Longitudinal Twin Study (N = 1116 pairs) to examine the
sex differences etiology of the association between low IQ (age 5) and the
development of antisocial behavior (age 7) in young children. IQ had a significant effect on the
development of antisocial behavior (r = -.17, p< .001). This effect was significantly stronger in
males (r = -.25, p< .001) than females (r = -.10, p< .05). Bivariate
twin model-fitting revealed that the etiology of the covariance between IQ
and antisocial behavior also differed in males and females. Common genetic influences explained 100%
of the covariance between IQ and antisocial behavior in males. Alternatively, non-shared environmental
influences explained 100% of the covariance in females. Findings are discussed in relation to
sex differences in the etiology of antisocial behavior.
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Yulia
Kovas1, Nicole Harlaar1, Stephen A. Petrill2,
and Robert Plomin1. Mathematics,
Reading, and IQ: A Multivariate genetic Analysis in 7-year-old Twins 3
1Social,
Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry,
King=s College London, UK, 2
Department of Biobehavioral Health, The Pennsylvania State University, USA, 3Supported
by the UK Medical Research Council (Grant G9424799)
Address :
SGDP Centre, PO 83, Institute of Psychiatry, De Crespigny Park, London, SE5
8AF, UK Telephone: +44 (0)207-848-5403
Fax: +44 (0)207-848-0895
Email: y.kovas@iop.kcl.ac.uk
Mathematics performance in the early school years has recently been
shown to be highly heritable as assessed by UK teachers following National
Curriculum criteria. To what extent
does this genetic influence on mathematics overlap with genetic influence on
reading and on general cognitive ability (g or IQ)? For 2,825 pairs of 7-year-old same-sex
twins, we used teacher assessments of mathematics performance, teacher
assessments of reading performance and the Test of Word Reading Efficiency
(administered by telephone), and a telephone-administered cognitive battery
(adapted form Wechsler Intelligence Scale for Children) to assess g. Strong correlations were found between
reading and mathematics (.70) and moderate correlations between mathematics
and g (.43) and between reading and g (.47). Multivariate
genetic analysis indicated substantial genetic overlap between mathematics,
reading and g - genetic correlations ranged between .62 and .76.
Nonetheless, fitting a trivariate Cholesky decomposition model to the data
revealed the existence of both common and independent genetic influences for
mathematics. That is, significant
mathematics-specific genetic variance was found, as well as significant
genetic variance specific to mathematics and reading but independent of g,
and significant genetic variance in mathematics in common with reading and
g. Shared and nonshared environmental influences only contributed modestly
to the specific and common variance for all measures. We conclude that the
same genes largely affect mathematics, reading, and g, although some
specific genetic and, to a lesser extent environmental influences, also
exist.
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Tomas S Kubarych, Michael C
Neale. Item analysis of structured
clinical interview data.
Department of Psychiatry,
Virginia Commonwealth University
Address : Box 980126 MCV
Richmond VA 23298-0126 USA
Most research in psychiatry
is based on structured clinical interviews, in which detailed Aprobe@ items are omitted unless
subjects respond positively to Astem@ items. Item-level data obtained from such an
instrument contain missing data which, if analyzed by methods that use listwise
deletion, restrict analysis to cases with at least one positive screen,
which may bias the results.
Inclusion of subjects who do not receive the probes, however,
introduces a class of subjects with zero variance on the probes.
Data from
relatives yield a proxy form of information that allows estimation of the
relationship between skipped items and the probes. Using data collected from adult female twins in Virginia, we
examined criteria for generalized anxiety disorder using a causal,
contingent, common pathway model.
Direct effects between stems and probes are first estimated. Multivariate analyses using similar
technology estimated the relationship between the stem and multiple probe
questions.
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Janine A Lamb1,
Elena Bonora1, Gaby Barnby1, Nuala Sykes1,
Elena Maestrini2, Francesca Blasi2, Elena Bacchelli2,
Kim S Beyer3, Sabine M Klauck3, Annemarie Poustka3,
Anthony J Bailey4, Anthony P Monaco1, International
Molecular Genetic Study of Autism Consortium (IMGSAC)5.
Towards
identification of autism susceptibility variants in the IMGSAC sample.
1Wellcome
Trust Centre for Human Genetics, University of Oxford, Oxford, UK, 2 University
of Bologna, Department of Biology, Bologna, Italy, 3Department of Molecular
Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany, 4 Section of Child and
Adolescent Psychiatry, Park Hospital for Children, Oxford, UK.
5 http://www.well.ox.ac.uk/~maestrin/iat.html
Autism is a severe
neurodevelopmental disorder, likely to arise on the basis of a complex
genetic predisposition. In order to identify susceptibility genes, the
IMGSAC has performed a genome screen for linkage in affected sibling pairs
(ASP) and identified putative susceptibility loci on chromosomes 2,7,9,16
and 17. These findings are supported in part by cytogenetic abnormalities in
autistic individuals and linkage findings from independent genome screen
studies. However, the peaks of linkage remain broad, often encompassing
hundreds of genes. In the absence of convincing association data, and in
order to improve localisation of linkage signals, researchers have made
efforts to reduce clinical and genetic heterogeneity. Analysis of the IMGSAC
data set according to ASP sex has provided evidence for sex-limited effects and
a possible parent-of-origin specific effect on chromosome 7. Functional
candidate genes mapping to the regions of linkage on chromosomes 2, 7 and 16
are being systematically screened to identify variants that may contribute
to autism aetiology. All coding regions and putative regulatory sequences
have been screened by DHPLC and sequencing in affected individuals from
families contributing to the linkage. The DNA variants identified have been
tested for association with autism by case-control and/or TDT studies in the
whole IMGSAC family sample. The finding of rare missense variants in the
Reelin gene on chromosome 7q22.1 and in cAMP-GEFII on chromosome 2q32
suggests that these two genes may have a role in autism aetiology in a small
proportion of cases, and requires further investigation. However, the clear
involvement of any gene(s) in the large proportion of IMGSAC families
remains to be established. Targeted high resolution association mapping
using a high density of single nucleotide polymorphisms across these regions
will enable advances towards the identification of autism susceptibility
genes.
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Kate Langley1,
Frances Rice1, Darko Turic1, Marianne Van den Bree1,
Michael, J. Owen1, Michael C. O’Donovan,1 Peter, A. Holmans1, Anita
Thapar1. Possible interaction between maternal smoking during
pregnancy and DRD4 genotype influencing severity of ADHD diagnosis2.
1Dept. of
Psychological Medicine, University of Wales College of Medicine, Cardiff,
United Kingdom. Supported by Wellcome Trust, SPARKS and ACTION RESEARCH. We
thank all the families, clinicians and field workers for their help
Address :
Department of Psychological Medicine, University of Wales College of
Medicine, 4th Floor, Heath Park, Cardiff, UK, CF14 4XN Telephone:
0044 (0)2920 742 934 Fax: 0044 (0)2920 747 839 Email: langleyk@cardiff.ac.uk
The 7-repeat
allele of a VNTR in the DRD4 gene has been found to be, significantly
associated with Attention Deficit Hyperactivity Disorder (ADHD) in a recent
meta-analysis (Faraone et al., 2001 American Journal of Psychiatry.158(7):1052-7. ).
Influence of environmental factors including maternal smoking during
pregnancy (Linnet et al., 2003 American Journal of Psychiatry;160(6):1028-40)
has also been recognised. We investigated possible interplay between DRD4
genotype and smoking during pregnancy and their association with diagnosis
of ICD-10 Hyperkinetic Disorder (HKD) which has been proposed as a more
severe, and possibly more neurobiological
manifestation of the disorder (Taylor et al, 1991, The
Epidemiology of Childhood Hyperactivity, Oxford University Press,
Oxford,UK).111 children aged 6-16 diagnosed with ICD-10, DSM-IV or DSM-III-R
ADHD participated in this study. All probands were genotyped for the DRD4
variant. Information regarding smoking during pregnancy was obtained
retrospectively from mothers. Main and interaction effects of DRD4 genotype
and smoking status were analysed using logistic regression and chi-square
analysis. Stepwise logistic regression analysis revealed that, although
there were no main effects of DRD4 or smoking status on ICD-10HKD diagnosis,
there was a significant statistical interaction between DRD4 genotype x
smoking (p=0.049, OR=2.288). Further analysis revealed that an association
between smoking and increased ICD-10HKD was only present in children with
the DRD4 7-repeat allele (7*-present, n=41, )2=5.306,
p=0.023, 7*-absent n=68, )2=0.402,
p=0.354). This analysis reveals a significant interaction between child=s DRD4 genotype and maternal smoking
during pregnancy which influences severity of ADHD diagnosis. When the
7-repeat susceptibility allele is present, it appears to moderate
association between maternal smoking during pregnancy and ADHD, resulting in
the more severe, narrower diagnosis of the disorder. This finding may have
significant implications regarding advice given to pregnant smokers, whilst
highlighting the importance of analysing genetic and environmental factors
together when investigating influences for ADHD.
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Henrik
Larsson1, Jan-Olov Larsson2, and Paul
Lichtenstein1. Differences in DSM-IV subtypes of ADHD: Genetic
and Environmental Influences.
1 Department of
Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm,
Sweden, 2 Department of Child &
Adolescent Psychiatry, The Karolinska Hospital, Stockholm, Sweden.
Address :
Box 281, SE-171 77 Stockholm, Sweden, Telephone: +46-8-524 87416 FAX:
+46-8-31 49 75, E-mail: Henrik.Larsson@meb.ki.se
Previous behavior genetic
studies of Attention-Deficit Hyperactive Disorder (ADHD) have not considered
the developmental changes in symptoms for individuals from childhood to
adolescence. Therefore, the aim of this study was to elucidate the
etiology of the development among and within the three subtypes of ADHD in
DSM-IV, primarily inattentive, primarily hyperactive-impulsive, and combined
subtypes.
We used a population-based
Twin study of Child and Adolescent Development (TCHAD) which comprises 1500
Swedish twins, first contacted when they were 8-9 years old and followed up
when they were 13-14 and 16-17 years old. Multivariate genetic analyses were
applied to study the importance of persistent, time-specific, and
subtype-specific genetic and environmental effects for parental-rated
symptoms of Inattention and Hyperactivity-Impulsivity.
The results suggested a
genetic factor influencing persistent symptoms of the combined type at all
three time-points (age 8-9, 13-14 and 16-17). Persistent subtype-specific
genetic and environmental factors were also important. Moreover, there
was a genetic factor specific to each time-point.
The
findings
support the DSM-IV conceptualization of the subtypes for ADHD. Genetic
influences explain in principle all variation for persistence in the
combined subtype, whereas both genes and environments are responsible for
the persistence of the Hyperactive-Impulsive and Inattentive subtypes. The
genetic time-specific variation in the expression of symptoms suggests that Aan immaturity factor@ and new
effects during and/or after puberty are also important.
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Jennifer Y.F. Lau1 and T. C.
Eley1. Adolescent depression: interactions, correlations and
cognitions2.
1 SGDP Centre, Institute of Psychiatry,
King=s College London, London,
UK, 2 The G1219 study was supported by the W T Grant
Foundation and by a Medical Research Council training fellowship to the
second author. The first author is supported by a Medical Research Council
doctoral studentship.
Address : SGDP Centre, Box PO 83, Institute
of Psychiatry, De Crespigny Park, London SE5 8AF Telephone: (00-44) 207 848
5414 Email: j.lau@iop.kcl.ac.uk
Emerging
evidence suggests that genetic and environmental factors interact (G x E)
and correlate (rGE) to produce vulnerability for adolescent depression (for
a review see J.Y. Lau and T.C. Eley, in press, Cur Psychiatry Rep, 6).
Consistent with these processes of interplay, a negative attributional style
is thought to interact with social stressors to precipitate symptoms (L.Y.
Abramson, M. E. Seligman, & J.D. Teasdale, 1978, J Abnorm Psychol, 87,
49-74) and to be influenced by parenting styles (J. Garber and C. Flynn,
2001, Cognit Ther Res, 25, 353-376), which may reflect both genetic
and environmental risks associated with parental genotype. Thus
attributional style may be involved in these risk mechanisms of interplay.
Self-reported data on attributional style, depression symptoms and maternal
negative control were collected from over 1300 adolescent twin and sibling
pairs, and used to examine two genetic models. The first tested for the
moderation of genetic risk to depression symptoms by negative maternal
control (G x E), whilst also specifying a genetic influence on this
environmental variable (rGE) (S. Purcell, 2003, Twin Res, 5. 554-571).
The second decomposed the phenotypic covariation between attributional style
and both depression and maternal negative control into genetic and
environmental influences. Initial results show that genetic effects on
depression are moderated by negative maternal control (G x E), and that
these genetic influences were also those implicated in the aetiology of this
parenting stressor (rGE). The second set of findings demonstrated roughly
equal proportions of genetic and environmental contributions to the association
between attributional style and depression. Similarly the covariation
between attributional style and maternal negative control also reflected
genes and environmental factors. These results reinforce the importance of
gene-environment interactions and correlations on adolescent depression.
Moreover, there is indirect support that a negative attributional style may
be involved in these risk mechanisms.
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Jeffrey M. Lessem1, Brett C.
Haberstick1, Christian Hopfer2, Andrew Smolen1,
David Timberlake1, John K. Hewitt1. Relation between
early use of marijuana and later illicit drug use in the Add Health sample.
1Institute for Behavioral Genetics,
University of Colorado, Boulder USA,
2Div. of Subst. Dependence, Univ. of Co. Health Sciences
Ctr., Denver. Supported by P01-HD31921 (PI: JR Udry), EY-12562 (PI: JK
Hewitt).
Address: Institute for Behavioral
Genetics, 447 UCB, Boulder, CO
80309-0447 USA Telephone: +1 (303) 492-2843 Email:
Jeff.Lessem@Colorado.EDU
In the Add Health study a school based
design was used to assess health related information on adolescents in
grades 7-12. Interviews were
conducted 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 was released in 2003. Marijuana use before the age of 17 was
found to be a significant predictor of illicit drug use at Wave III, when
the mean age of the sample is 22 years old.
The variance in marijuana use before age 17 is due to genetic, shared
environmental, and non-shared environmental factors, while the variance in
use of illicit drugs at Wave III is due to genetic and non-shared
environmental factors.
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Kate J Lifford1,
K. Langley1, D. Turic1, M. B. Van den Bree1,
J. Williams1 , M. J. Owen1 & M. C. O=Donovan1
A. Thapar1. Assessing the influence of GRIN2A on reading ability
in attention-deficit/hyperactivity disorder2.
1Department
of Psychological Medicine, University of Wales College of Medicine, Cardiff,
UK, 2Data collection funded by Wellcome Trust. Kate Lifford
sponsored by Biostatistics/Bioinformatics Unit (funded by Higher Education
Funding Council for Wales).
Address:
Department of Psychological Medicine, University of Wales College of
Medicine, Heath Park, Cardiff, CF14 4XN Telephone: 029 20742934 Fax: 029
20747839 Email: liffordkj@cardiff.ac.uk
One of the regions
of linkage suggested in a genome-wide scan for
attention-deficit/hyperactivity disorder (ADHD) and reading disability is on
chromosome 16p (S. K. Loo et al, 2003, Molecular Psychiatry,
1-9). GRIN2A, a gene found in this
region, is a candidate gene in which a polymorphism on exon 5 has been found
to be associated with ADHD (D. Turic et al, 2004, Molecular Psychiatry,
9, 169-173). This study included 161 ADHD children, a subset of the
sample in which the association with GRIN2A has been found. Reading ability
was measured in this sample using mean score of the three sub-tests of the
Weschler Objective Reading Dimension (Weschler, 1993, The Psychological
Corporation, UK). Multiple regression analysis showed that association of
the allelic variation of the GRIN2A polymorphism with reading score was not
significant (F(1, 129) = 0.182, p=0.670). The genetic variation
in GRIN2A therefore does not appear to account for phenotypic variation in
reading ability in children with ADHD.
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Michelle Luciano1,
Mark Wainwright1, Margaret J. Wright1, Gina M. Geffen2,
David L. Duffy1, Nicholas G. Martin1. Using
multivariate linkage methods to locate QTLs for word recognition and IQ3.
1 Genetic
Epidemiology, Queensland Institute of Medical Research, Brisbane,
Queensland, Australia, 2 Cognitive Psychophysiology Laboratory,
University of Queensland, Brisbane, Queensland Australia, 3 Collection
of phenotypes and DNA sample was supported by grants from the Australian
Research Council and the Human Frontier Science Program. The genome scans
were supported by the Australian NHMRC=s Program
in Medical Genomics [NHMRC-219178] and a grant to Dr Jeff Trent from the
Center for Inherited Disease Research at Johns Hopkins University. CIDR is
fully funded through a federal contract from the National Institutes of
Health to The Johns Hopkins University, Contract Number N01-HG-65403.
Address :
Genetic Epidemiology, Queensland Institute of Medical Research, PO Box Royal
Brisbane Hospital, 4029, Herston Australia Telephone: +61 7 3362 0218, Fax:
+61 7 3363 0101, Email: michelLu@qimr.edu.au
In a sample of 500
adolescent twin pairs we have previously shown that the covariation between
IQ subtest scores and tests of word recognition is primarily mediated by
genes. While most of the genetic
variance in IQ (29-57%) and whole-word reading (30-40%) measures is
explained by this common genetic factor, unique genetic influences are also
significant (M. Wainwright et al, in press, Behav. Genet.). Our aim now is to find QTLs influencing
the variation in these measures. DNA
has been collected from twins, their siblings and available parents
(>80%) and a genome scan of 400-761 autosomal markers has been completed
for 342 families (includes between 2 and 5 siblings) with IQ and reading
phenotypes. Here we report our first
results for multivariate genome-wide linkage of IQ (Multidimensional
Aptitude Battery: verbal and performance scales) and word-recognition
(Schonell Graded Word Reading Test, Cambridge Contextual Reading Test)
measures. In a genome-wide linkage
analysis of reading and language-related phenotypes, multivariate methods
were shown to confer greater statistical power compared to the univariate
case (A.J. Marlow et al., 2003, Am. J. Hum. Genet.,72,
561-570). Our findings also find
support for advantages of multivariate over univariate linkage methods,
generally confirming gains in power plus the moderation of apparent biases
to a single phenotype. Suggestive
linkage on the long arm of chromosome 2 was indicated. We intend to broaden our range of reading
measures to include tests which tap diverse components of reading processing
(orthographic skill & phonological decoding) and are predictive of
reading disability subtypes.
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Stacy K. Lynch1,
Eric Turkheimer1, Robert E. Emery1, Brian M. D=Onofrio1,
Jane Mendle1, Wendy S. Slutske2, Andrew C. Heath3,
& Nicholas G. Martin4. A Genetically
Informed Study of the Association Between Harsh Punishment and Offspring
Behavioral Problems
1Department
of Psychology, University of Virginia, Charlottesville VA USA. 2Department of
Psychology, University of Missouri B Columbia,
Columbia MO USA, 3School of Medicine, Washington University, St.
Louis MO USA, 4Queensland Institute of Medical Research,
Brisbane, Australia. Supported by William T. Grant Foundation, Grant # 2054
Address :
Dept. of Psychology, Box 400400 University Of Virginia
Charlottesville,
VA 22903 USA Telephone: (434)
962-2836
E-mail: akl8t@virginia.edu
Although harsh
punishment styles have been associated with a variety of negative outcomes
in children, the definition of harsh punishment remains inconsistent. Moreover, studies of the putative causal
effects of harsh parenting on children have been hindered by uncontrolled
third variables and environmental contexts.
The present study uses a children of twins design to analyze the
consequences of various degrees and definitions of punishment, ranging from
mild non-physical punishment to abusive physical punishment. Forms of punishment associated with high
levels of offspring pathology are further examined within a hierarchical linear
modeling (HLM) framework, which facilitates the discriminate of any specific
effects of punishment style from genetic or environmental variables that may
confound the relationship. Results
indicate that corporal punishment in general does not have significant
associations with negative childhood outcomes, but other more harsh forms of
physical punishment do appear to have specific causal effects.
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Faïza Ben Mabrouk, Edouard
Pearlstein, Jean-Françios Pflieger and Laurent Vinay. Serotoninergique
shaping of the locomotor pattern in the in vitro neonatal rat spinal
cord.
ADDRESS :
CNRS, Marseille, Plasticité et Physiopathologie de la Motricité, UMR 6196
CNRS / Université de la Méditerranée 31, Chemin Joseph Aiguier 13402
Marseille Cedex 20, France Email : faiza@dpm.cnrs-mrs.fr
The serotoninergic
projections from raphe nuclei arrive in the lumbar enlargement of the spinal
cord during the late fetal period in the rat, a time window during which the
locomotor pattern switches from left/right (L/R) and flexor/extensor (F/E)
synchrony to alternation. The goal of the present study was to investigate
the role played by serotonin (5-HT) in shaping the locomotor pattern, i.e.
L/R and F/E alternations. Fictive locomotion was induced by bath application
of N-methyl-D,L-aspartate (NMA) in the in vitro neonatal rat spinal
cord preparation. By means of cross-correlation analysis we show that 5-HT,
when added to NMA, strengthens L/R and F/E
(recorded from the 3rd and 5th lumbar ventral
roots, respectively) alternations. This effect was partly reproduced by
activation of 5-HT2A/2C receptors[-]. In a last series of
experiments, we tested the contribution of endogenous 5-HT to NMA-induced
fictive locomotion. Reducing the functional importance of endogenous 5-HT,
either by inhibiting its synthesis with daily injections of
p-chloro-phenylalanine (PCPA), starting on the day of birth, or by
application of ketanserin (á 5-HT2 receptor antagonist) or
SB269970 (á 5-HT7 receptor antagonist), disorganized the
NMA-induced locomotor pattern. This pattern was restored in PCPA-treated
animals by adding 5-HT to the bath. These results demonstrate that 5-HT is
critical for shaping the locomotor pattern in the neonatal rat. This action
may be exerted through a potentiation of reciprocal inhibitory connections.
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Hiroko Maekawa1,
Juko Ando2, and Yutaka Ono3. The structure of eating
behavior and attitudes among Japanese adolescent women.
1Department
of Education, Graduate school of human relations, Keio University, Minato-ku
Tokyo Japan, 2 Faculty of letters, Keio University, Minato-ku
Tokyo Japan, 3 Health Center, Keio University, Yokohama Kanagawa
Japan.
Address :
5-19-9-304, Nishikamata, Ota-ku, Tokyo 144-0051 Japan
Telephone: 81 3
3734 5125 Email: hm-hiro@pop21.odn.ne.jp
Recent research
has indicated that most of Japanese adolescent women think themselves fat,
and they want to be thinner, although, in reality they are thinner than they
were 20 years ago. It has been known that the weight and shape concerns are
the risk factors of eating disorders. Many studies about disordered eating
behavior have been conducted, but the genetic and environmental structure of
eating behaviors and attitudes is unclear. To reveal the structure of eating
behaviors and attitudes, 416 adolescent female twins (MZ:316 pairs, DZ:100
pairs) from the Keio Twin Project were examined with the Eating behavior
Eating Disorder Inventory (EDI; Garner, Olmsted, & Polivy, 1983) which
assessed Drive for Thinness, Bulimia, and Body Dissatisfaction. The pairs whose
BMI is over 25 were excluded to examine the structure of eating behavior and
attitudes among women who don=t need to
lose their weight. Results obtained from Cholesky decomposition indicated
that a substantial amount of the covavriance between Drive for Thinness,
Bulimia, and Body Dissatisfaction was accounted for by an additive genetic
factor. Specifically, additive genetic factor accounted for approximately
64% of the covariance between Drive for Thinness and Bulimia, 60% of the
covariance between Drive for Thinness and Body Dissatisfaction. Non-shared
environmental factor accounted for 36% and 40%, respectively. In contrast,
the covariance between Bulimia and Body Dissatisfaction was accounted for
97% by non-shared environmental factor. The results showed that additive
genetic factor made the largest contribution to the covariation among eating
behaviors and attitudes.
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Hermine H. Maes,
Michael C. Neale, Judy L. Silberg, Debra L. Foley, Lindon J. Eaves1.
Genetic and environmental transmission of retrospective conduct disorder2.
1Virginia
Institute for Psychiatric & Behavioral Genetics, Department of Human
Genetics and Psychiatry, Virginia Commonwealth University, Richmond VA
23298, USA, 2Supported by NIH grants HL60688, MH45268, MH55557
and MH57761.
Address : VIPBG, MCV/VCU,
P.O. Box 980003, Richmond VA 23298-0003 Telephone: 804 828 8145 Fax: 804 828 8801 Email: hmaes@vipbg.vcu.edu URL: http://www.vipbg.vcu.edu
With the recent
attention on gene by environment interactions including parental treatment,
it is important to disentangle genetic from cultural transmission of
antisocial behavior. The classical
twin design augmented with parental data on the same phenotype allows such a
partitioning of variance . The goals
of this study were to quantify the genetic and non-genetic sources of
inter-generational transmission for conduct disorder and to extend the
twin-parent design to include biological and non-biological parents. Data on conduct disorder before age 18
(retrospective conduct disorder) from the Young Adult Follow Up (YAFU) of
the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were
analyzed using Mx. Given a quarter
of the parental informants in the VTSABD are non-biological, we extended the
twin-parent model to include not-related caregivers. Familial resemblance for retrospective
conduct disorder was explained by additive genetic (h2~35%) and
shared environmental factors (c2~20-30%) in biological
families. Including the
non-biological parents resulted in a moderate increase in heritability and
decrease in the shared environmental contribution. While cultural transmission parameters could be dropped
without loss of goodness-of-fit, assortative mating was significant. Sex differences were more pronounced for
non-parental shared environment. We
conclude that genetic factors accounted for the majority of the
parent-offspring transmission of retrospective conduct disorder.
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Sergei B. Malykh1, Elena D.
Gindina1, Viktoria V. Nadyseva1. The developmental changes
in sources of individual differences in adolescent temperament.
1Laboratory of Developmental Behavior
Genetics, Psychological Institute of Russian Academy of Education, Moscow,
Russia
Address: Psychological Institute of
Russian Academy of Education, Mokhovaya street, 9 AV@, Moscow, 125009 Russia
Telephone: +7(095)202-9363 Fax +7(095)134-2119 Email: malykh@pirao.ru
The study was performed as a part of a
Moscow longitudinal twin project and aimed to explore genetic and
environmental contributions to temperament of Russian adolescents in
pubertal and post-pubertal periods. 53 pairs of monozygotic (MZ) and 55
pairs of same-sex dizygotic (DZ) Russian twins completed the children
version of the Structure of Temperament Questionnaire (C-STQ; Rusalov, V.M.,
Oprosnik struktury temperamenta. [A Temperament Structure
Questionnaire.] Methodological manual, Moscow: Smysl, 1992. In Russian.) at
the age of 12-14 years and four years later. The correlation and model
fitting analysis showed significant differences in the degree of genetic
determination of temperament dimensions in two age periods. At the age of
12-14 years, significant genetic influences were revealed only on 3 of the
C-STQ dimensions - Social Tempo, Emotionality and Social Emotionality. The
best fitting model for these traits was simple genetic model. The
heritability estimates for Social Tempo, Emotionality and Social
Emotionality were 60%, 66% and 66% - respectively; the remaining variance
was explained by non-shared environment effects. Individual differences in
the other C-STQ dimensions were due to environmental factors. At the age of
16-18 years, evidence for moderate to high genetic influence was seen for
all C-STQ dimensions. Under the best fitting simple genetic model, the
genetic influences accounted for 64% of the variance in Object-related
Ergonicity, 42% - in Social Ergonicity, 27% - in Object-related Plasticity,
40% - in Social Plasticity, 32% - in Object-related Tempo, 47% - in Social
Tempo, 43% - Object-related Emotionality and 37% - in Social Emotionality.
Non-shared environmental effects explained the rest of the total variance in
these dimensions. A substantial increase in genetic influences and a
declining influence of shared environmental factors during the transition
from pubertal to post-pubertal period was related to decline of temperament
resemblance among DZ twins.
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Carol A Manning1,
Lillian J Currie1, Madeline Harrison1, G. Frederick
Wooten1, and Eric N. Turkheimer2. Intellectual
Impairment Differences in Parkinson=s Patients
With And Without Affected Mothers2.
1Department
of Neurology, University of Virginia, Charlottesville, VA USA, 2Department
of Psychology, University of Virginia, Charlottesville, VA USA, 3Supported
by the American Parkinson's Disease Association Advanced Center for
Parkinson's Research B
University of Virginia and Morris K. Udall Parkinson's Disease Research
Centers of Excellence (NINDS-P50-NS39788).
Address :
Department of Neurology, Box 800394, University of Virginia,
Charlottesville, VA 22908 Phone: (434) 982-1012 Fax: (434) 982-1996
Email: cm4r@virginia.edu
Genetic factors
play a role in the expression of Parkinson=s Disease
(PD) but the mechanism of inheritance remains unclear (Currie LJ. Harrison MB.
Trugman JM. Bennett JP. Swerdlow RH. Manning CA. Wooten GF in Journal of
Neurology, Neurosurgery & Psychiatry. 71(1):130-1, 2001 Jul; Marder
K. Levy G. Louis ED. Mejia-Santana H. Cote L. Andrews H. Harris J. Waters C.
Ford B. Frucht S. Fahn S. Ottman R. in Annals of Neurology. 54(4):507-13,
2003 Oct). In addition,
intellectual impairment is being recognized as an important clinical feature
in some individuals with PD.
Although intellectual impairment has been associated with increased
age of onset, little is known about the relationship between inheritance of
PD and cognitive symptoms. We
examined intellectual impairment in our database of 629 carefully
characterized individuals with PD.
Patients were organized into three groups of probands: 1) PD patients
with an affected mother (N=45), 2) PD patients with an affected father (N=
33) and 3) PD patients without a first-degree relative with the disease (N =
551). The average age at disease
onset, number of years with the disease, and overall disease severity as
measured by the Unified Parkinson=s Disease
Rating Scale (UPDRS) were similar for all groups. Logistic regression
revealed that probands with an affected mother were significantly more
likely to have intellectual impairment, as measured by the UPDRS, than were
probands without an affected mother (p <0.05). However, the groups did not differ in severity of motor
symptoms, degree of depression or presence of thought disorder. These results suggest that disease
phenotype is related to mode of inheritance and that maternal inheritance of
PD is associated with an increase in cognitive symptoms.
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Cecilia Marino1, L Vanzin1, R Giorda1, A Frigerio1, M L Lorusso1, M Nobile1, M Molteni1, M Battaglia2. An assessment of
transmission disequilibrium between quantitative measures of childhood
problem behaviors and DRD2/TaqI, DRD2/-141C Ins/Del and DRD4/48bp-repeat
polymorphisms.
1 Eugenio Medea Scientific
Institute, Department of Child Psychiatry, Bosisio Parini, Italy, 2 San Raffaele Scientific
Institute, Milan, Italy.
Address: Eugenio Medea
Scientific Institute, Department of Child Psychiatry, Via Don Luigi Monza
20, Bosisio Parini, Lecco, Italy. Tel ++39-031-877-381 cmarino@bp.lnf.it
In a pilot study of 120
children with reading disabilities we assessed the presence of linkage
disequilibrium between the DRD2/TaqI and the DRD4/48bp-repeat polymorphisms
and quantitative measures of behavioral problems derived from parental rated
Child Behavior Checklist (CBCL) (Achenbach, T.M. Manual for the CBCL/4-18
and 1991 Profile, 1991. Burlington, VT: University of Vermont Department of
Psychiatry).
Analyses included measures
of between-individuals association, and a test of the presence of linkage
disequilibrium by a logistic regression-based extension of the Transmission
Disequilibrium Test (logistic regression QTDT) (Waldman, I.D., Robinson,
B.F., Rowe, D.C.,1999, Ann. Hum. Genet. 63: 329-340). In
between-individuals association analyses the AWithdrawn@ scale of CBCL was related
to the number of risk alleles of DRD4 and the ASocial Problem@ scale was associated with
the number of risk alleles of DRD2 (the 7-repeat and the A1 allele
respectively were considered the risk alleles). Logistic regression QTDT
yielded statistically significant evidence in favor of linkage
disequilibrium between DRD2 and ASocial Problems@ (Wald χ2= 4.13, df=1, p= .042, Odds
Ratio= 1.97). No linkage disequilibrium was found for AWithdrawn@ and DRD4 (Wald χ2= 2.64, df=1, p= .1, Odds
Ratio= 1.44). Although preliminary, these findings are in harmony with
previous data that suggest a role of the same polymorphism in influencing
individual sensitivity to reward and response to social clues and
reinforcements in man and animal (Blum, K., Braverman, E.R., Holder, J.M.,
Lubar, J.F., Monastra, V.J., Miller, D., Lubar, J.O., Chen, T.J., Comings,
D.E., 2000, J. Psychoactive Drugs. 32 Suppl:i-iv, 1-112). To further
investigate the imporance of the DRD2 gene, quantitative haplotype analyses
were run with haplotype B141C Ins/Del-DRD2/TaqI and
dimensions of the CBCL (Horvath S., Xu X., Lake S.L., Silverman E.K., Weiss
S.T., Laird N.M., 2004, Genet Epidemiol. 26, 61-9).
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Nicholas G.
Martin, Gu Zhu, David L. Duffy. A genome scan for eye color using a full
two-locus model
Queensland
Institute of Medical Research, Brisbane, Australia. Collection of phenotypes
and DNA samples was supported by grants from the Queensland Cancer Fund, the
Australian National Health and Medical Research Council, and the U.S.
National Cancer Institute (CA88363).
The genome scans were supported by the Australian NHMRC=s Program in Medical Genomics
[NHMRC-219178] and a grant to Dr Jeff Trent from the Center for Inherited
Disease Research at Johns Hopkins University. CIDR is fully funded through a
federal contract from the National Institutes of Health to The Johns Hopkins
University, Contract Number N01-HG-65403.
Address : QIMR,
Brisbane 4029, Australia, fax 61-7-3362 0101, Telephone 61-7-3362
0278, Email: nickm@qimr.edu.au
We have rated eye
colour on a three point scale (1 = blue/grey, 2 = hazel/green, 3 = brown) in
502 twin families and carried out a 5-10cM genome scan (400-757
markers). We analysed eye colour as
a threshold trait and performed multipoint sib pair linkage analysis using
variance components analysis in Mx.
A lod of 19.2 was found at the marker D15S1002, less than 1cM from
OCA2, which has been previously implicated in eye colour variation. We
estimate that 74% of variance in eye colour liability is due to this QTL and
a further 18% due to polygenic
effects. However, a large shoulder on this peak suggests that other loci
affecting eye colour may be telomeric of OCA2 and inflating the QTL
estimate. No other peaks reached genome-wide significance, although lods
>2 were seen on 5p and 14q and lods>1 were additionally seen on chromosomes
2, 3, 6, 7, 8, 9, 17 and 18. Most of
these secondary peaks were reduced or eliminated when we repeated the scan
as a two locus analysis with the 15q linkage included, although this does
not necessarily exclude them as false positives. We also estimated the interaction between the 15q QTL and the
other marker locus but there was only minor evidence for additive x additive
epistasis. Elaborating the analysis to the full two locus model including
non-additive main effects and interactions did not strengthen the evidence
for epistasis. We conclude that most variation in eye colour in Europeans is
due to polymorphism in OCA2 but that there may be modifiers at several other
loci.
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Motoko Matsuura1,
Masumi Sugawa2, Atsushi Sakai3, Taketoshi Takuma4,
Sachiko Amou5. Genetic and environmental influences on career
attitudes and vocational preparation in Japanese junior high school and high
school students.
1Development
of Human Developmental Science, Graduate School of Human Culture, Ochanomizu
University Japan, 2Department of Psychology,
Faculty of Letters and Education, Ochanomizu University Japan, 3Department
of Psychology and Education, Faculty of Education Human Science, University
of Yamanashi Japan, 4Graduate School of clinical psychology,
Tokyo International University, 5Aoyama Institute of Education
Japan.
Address :
3-26-12-305, Futaba, Shinagawa-ku,Tokyo,142-0043, Japan Telephone:03 5978
5279 Fax:03 5978 5270 E-mail: g0370324@edu.cc.ocha.ac.jp
This study
examined the genetic and environmental contributions on career attitudes and
vocational preparation . The Japanese twin sample of junior high school and
high school students (120 pairs of MZ and 99 pairs of DZ ) completed the
questionnaires about their career attitudes and the level of their vocational
preparation. Univariate genetic analyses were indicated that CE models
yielded the best fit in both of career attitudes and vocational preparation.
This study showed that eating attitudes and behaviors were influenced by
gender and age differences.
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John J. McArdle 1
and Fumiaki Hamagami 1. The addition of biometric components to
longitudinal dynamic structural models of growth and survival2.
1
Department of Psychology, University of Virginia, Charlottesville VA USA, 2
Supported by NIH Research Grant #AG-07407 from the National Institute
on Aging.
Address :
P.O. Box 400400, University of Virginia, Charlottesville VA 22904 USA
Telephone: (434) 924-0656; Fax: (434) 982-4766; Email: jjm@virginia.edu
There are now a
number of studies in human aging research where longitudinal data have been
collected on adults who are twins or members of the same families (e.g.,
SATSA). The analyses of these longitudinal data initially emphasized the
description of patterns of growth and change over time, including the
estimation of biometric sources of variation. In more recent analyses, there has been an emphasis on age as
a focal basis of change, an effort to understand the lead-lag relationships
across different phenotypes and genotypes, and the importance of accounting
for survival (mortality) of individuals and families. In this presentation
we examine some ways in which all of these components can be estimated in a
joint analysis of the same longitudinal data. The structural models of
growth and change are based on the recent approach for longitudinal twin
data presented in McArdle & Hamagami (Behavior Genetics, 33
(3): 137-1592003). The survival-frailty models for twin data are initially
based on the recent work of Yashin, Iachine, & Harris (Behavior
Genetics, 29 (1):11-19, 1999). We next consider several recent
proposals for combining latent growth and survival models, including the
useful overview of Lin, McCulloch, & Mayne (Statistics in Medicine,
21: 2639-2382, 2002) and the recent contributions of Guo & Carlin
(American Statistician, 58 (1): 1-9, 2004). We highlight the
latter because standard software for maximum likelihood estimation is
presented (i.e., NLMIXED, winBugs). To combine the most useful features of
all longitudinal models we: (1) add biometric components to the
growth/survival components, (2) examine several alternative models for their
inter-relationships, (3) illustrate the accuracy and reliability of this
approach using standard software, and (4) examine a few simpler but
practical alternatives. Our results highlight both the potential benefits
and the potential limitations of integrated structural analyses based of all
these popular longitudinal considerations.
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Matt McGue1,
Margaret Keyes1, Irene Elkins1 & William G Iacono1.
Shared Environmental Effects B Do They
Endure?
1Department
of Psychology, University of Minnesota. Supported by NIAAA grant # AA11886
Address : 75
East River Road, Minneapolis, Minnesota 55455 USA
In 1987, Plomin
and Daniels showed that siblings growing up in the same home bore little
psychological similarity to one another if they were not genetically
related. This provocative observation has stimulated much research, which is
generally supportive of the general conclusion that shared environmental
influences are minimal or non-existent. Two behavioral domains, cognitive
abilities and antisocial behavior, appear to run counter to the general
conclusion regarding the relative unimportance of shared environmental
effects. Nonetheless, it remains unclear whether shared environmental
effects on these behaviors endure much beyond the period of common rearing.
Using data from the ongoing follow-up of a large cohort of adoptive sibling
pairs we will explore evidence for the durability of shared environmental
effects. We will interpret study findings in the context of evolving notions
of the nature of family socialization.
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Sarah Medland1,2,
Danuta Loesch3, Bogdan Mdzewski4, Gu Zhu1,
Nicholas G Martin1. A multivariate genome scan for
finger ridge count.
1Queensland
Institute of Medical Research, Australia, 2University of
Queensland, Australia, 3La Trobe University Australia, 4 Bogdan
Mdzewski died on the 30/11/2001. Collection of
phenotypes and DNA samples was supported by grants from the Australian
National Health and Medical Research Council. The genome scans were supported by the Australian NHMRC=s Program in Medical Genomics
[NHMRC-219178] and a grant to Dr Jeff Trent from the Center for Inherited
Disease Research at Johns Hopkins University. CIDR is fully funded through a
federal contract from the National Institutes of Health to The Johns Hopkins
University, Contract Number N01-HG-65403.
MAIL: QIMR, Brisbane 4029, Australia, fax
61-7-3362 0101, phone 61-7-3845 3551, email: sarahMe@qimr.edu.au
Previous genetic
studies of finger ridge count have typically found that ridge count is
influenced both by a common genetic factor (that influences the magnitude of
ridge count on all ten fingers) and by a series of independent factors or
developmental fields that take into account the correlation in ridge count
which is highest between adjacent fingers. We performed a 5-10cM
multivariate genome scan (400-761 markers) on the ridge count of individual
fingers in a sample of 486 twin families. In the multivariate genome scan we
estimated 5 QTL effects (one for each of the five digits, with the QTL
estimates of corresponding fingers on the left and right hands constrained
to be equal). The results of these analyses were compared to those of a
univariate QTL analysis for Total Finger Ridge Count (a summary measure in
which the ridge counts from all fingers are weighted equally). We found that
the univariate analysis performed better than the multivariate analysis when
the QTL effect loaded equally across all fingers (as seen on 1q43). However,
the multivariate analysis conferred greater statistical power when the
estimates of the QTL effects behaved in a manner consistent with a
developmental field (ie as seen on 3q25 and 7p15). Our findings provide
evidence for the suggestion that both common genetic factors and
developmental fields may influence the development of dermatoglyphic
characteristics.
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Jane Mendle1,
Eric Turkheimer1, Robert E. Emery1, Brian M. D=Onofrio1,
Stacy K. Lynch1, Wendy S. Slutske2, Andrew C. Heath3,
& Nicholas G. Martin4. Association of Early Menarche with
Adolescent Depression4.
1Department
of Psychology, University of Virginia, Charlottesville VA USA, 2Department
of Psychology, University of Missouri B Columbia,
Columbia MO USA, 3School of Medicine, Washington University, St.
Louis MO USA, 4Queensland
Institute of Medical Research Australia, 5Supported by William T.
Grant Foundation, Grant # 2054.
Address :
Dept. of Psychology, Box 400400, University Of Virginia Charlottesville, VA
22903 Telephone: (434) 982-5573
E-mail: jm4ky@virginia.edu
Early onset of
menarche is associated with increased risk for depression, eating disorders,
and substance abuse during adolescence.
It has been posited that the emotional and psychological stress
related to non-normative pubertal timing plays a causal role in the etiology
of these disorders. Since cognitive
and physical development do not necessarily occur in synchrony, precocious
physical maturation may increase the likelihood that girls will be forced to
confront new environments, stressors, and social expectations before they
are emotionally prepared to do so.
It may also be that those girls who exhibit obvious signs of physical
maturation may find it difficult to maintain friendships with same-sex peers
who have not developed at a similar rate.Given that menarche and pubertal
timing are strongly influenced by familial factors, the association between
early menarche and adolescent psychopathology may be muddied by genetic and
environmental confounds. The primary
purpose of this study is to clarify whether early menarche wields a pure,
causal effect on the development of depression during adolescence. Using data from the Australian National
Health and Medical Research Council Twin Registry, we will conduct a cotwin
control analysis of age of menarche and development of depressive
symptomatology utilizing a sample of twins comparatively discordant for
menarcheal age. If early pubertal
timing has a causal influence on depressive etiology, the earlier maturing
twin will be more likely to develop depression than the later maturing
one. However, if some confound
associated with familial propensity to develop depression and pubertal
timing exists, there will be no difference in the emergence of adolescent
depression between the twins.
Additional analyses will model the inclusion of potential
mediators of depression into hierarchical linear models.
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Christel M.
Middeldorp1,2, Danielle C. Cath2, A. Leo Beem1,
Dorret I. Boomsma1. Genetic epidemiology of depression in a
selected population of Dutch twins and their siblings.
1Department
of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The
Netherlands, 2Department of Psychiatry, GGZ Buitenamstel / Vrije
Universiteit Amsterdam, Amsterdam, The Netherlands, 3Supported by
ZonMW Grant 940-37-024.
Address: Vrije Universiteit Amsterdam, Dep
Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The
Netherlands Telephone: +31-20-4448787 Fax: +31-20-4448832 Email: cm.middeldorp@psy.vu.nl
A multivariate genetic analysis
on the anxiety, depression, neuroticism and somatic-anxiety data collected
in twins and their siblings of the Netherlands Twin Register (NTR) revealed
that genetic covariances for these traits could be fully attributed to a
common genetic factor (D.I. Boomsma, A.L. Beem, M. van den Berg, C.V. Dolan,
J.R. Koopmans, J.M. Vink, E.J.C. de Geus and P.E. Slagboom, 2000, Twin
Research 3, 323-334). The value of this common genetic factor can
be estimated for each individual using the individual scores on the traits
and the factor loadings on the common genetic factor. Based on these genetic
factor scores (GFS), available for 7770 twins and their siblings from 3323
families, a selection was performed to obtain a sub-sample that is most
informative for linkage studies. Of the selected subjects, 1256 twins and
their siblings from 478 families also participated in a Telephone interview
during which the Composite International Diagnostic Interview (CIDI) (World
Health Organization, 1997, CIDI-Auto, Version 2.1: Administrator=s guide. World Health
Organization, Sydney, Australia) was administered. We will present the
genetic epidemiological analysis of the liability for major depressive
disorder in an extended twin design. Because the sample was selected based
on the GFS, bivariate genetic analyses will be carried out for major
depression, our variable of interest and the GFS, the variable used for the
selection (R.J.A. Little and D.B. Rubin, 1987, Statistical analysis with
missing data. Wiley, New York, USA).
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Michael Miller.
Linkage
Conditional on Measured Genotypes Under Conditions of Low Statistical Power
Division of
Epidemiology, University of Minnesota, USA. Email: mbmiller@taxa.epi.umn.edu
Almasy and Blangero (Behavior Genetics,
March 2004) demonstrated that when there is a single QTL in a chromosomal
region and a significant LOD-score peak (LOD > 3.0) is observed in that
region, use of the QTL as a covariate in the linkage analysis usually
reduces the peak to a non-significant level (LOD < 0.588) at the QTL.
Thus, one may test a candidate gene as a covariate in quantitative linkage
analysis to see if it accounts for an observed peak. The simulation
undertaken by Almasy and Blangero was highly powered with a QTL accounting
for 28% of the trait variance, a mean LOD-score of 5.57 and 87% of
replicates achieving LOD > 3.0. It is more realistic to simulate data
with a QTL that accounts for much less variance (maybe 10%) and produces
much lower statistical power. When we analyze sibling-pair data simulated
under such a model, we find that using the QTL as a covariate will rarely
reduce a statistically significant peak (LOD > 3.0) to nonsignificance
(LOD < 0.588). We also show through simulation that this finding is due to
the fact that much of the contribution to the LOD-score peak comes from
lucky associations of extra-QTL genetic effects and random environmental
influences with identity-by-descent patterns. Such effects remain when the
QTL is used as a covariate. Our findings imply that the method recommended
by Almasy and Blangero works differently, and is less definitive, when power
is low to detect the effect of the QTL. Alternative methods and
interpretations are recommended.
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Maria Napolitano, Thalia C. Eley1.
Parental disciplinary styles and associations with anxiety in adolescent and
young adults2.
1 MRC, Social, Genetic and Developmental
Psychiatry Research Centre, Institute of Psychiatry, London UK, 2 Supported
by an MRC career development award to the second author.
Address: MRC, SGDP, PO80, Institute of Psychiatry, De Crespigny Park,
London, SE5 8AF Telephone: 44 (0)207 848 0979 Email:
m.napolitano@iop.kcl.ac.uk
Minimal attention
has been paid to the association between aspects of anxiety and parenting
and, to our knowledge, this has not been examined within a behavioural
genetic design. This study considers the importance of parental disciplinary
styles as risk factors for adolescent anxiety symptoms. Perceptions of
maternal and paternal punitive and constructive discipline (M. Hetherington
& Clingempeel, 1992, Monographs of the society for research in Child
Development, 57, 2-3) were assessed from over 1,300 pairs of
adolescents and young adults twins and siblings (age range 13-21 years). In
addition the young people completed 6 anxiety scales: panic, separation
anxiety, social anxiety, physical injury anxiety, ocd, and general anxiety.
(S. Spence, 1990, Multivariate Behavioral Research, 25,
175-180). The results indicated a significant interaction between age and
sex on the anxiety scale; for females, increasing age predicted higher
anxiety scores. Univariate genetic analyses indicated that all the anxiety
scales were highly heritable (e.g. panic h2 = .48), with
indications of non-additive genetic influence. In contrast, the parental
discipline variables were less heritable and also influenced by the shared
environment (e.g. paternal constructive discipline h2 = .28 and c2
= .21). All anxiety and parental discipline variables varied as a function
of sex, and most by age. Associations between anxiety and perceptions of
parental discipline were higher for adolescent females (aged 11-15) than
adolescent males or young adults (aged 16-21). In the adolescent females,
associations between perceived maternal punitive discipline and general
anxiety, panic, social anxiety and OCD were highest (range r = .20-.26).
Bivariate genetic analyses on the adolescent females indicated that the
associations between perceptions of maternal punitive discipline and anxiety
sub-types were largely genetically influenced. These results suggest that
links between anxiety vary as a function of age and sex during adolescence
and young adulthood.
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Michael C.
Neale1. Extensions of models for genetic linkage: mixture
distributions and epistasis.
1 Virginia
Institute for Psychiatric & Behavioral Genetics, Department of
Psychiatry, Virginia Commonwealth University, Richmond VA 23298 USA, 2Supported
by NIH grants RR-08123, MH-01458 and MH-65322.
Address: VIPBG, MCV/VCU, P.O.
Box 980126, Richmond VA 23298-0126 USA Telephone: 804/828-3369 Fax:
804/828-1471 Email: neale@hsc.vcu.edu Web: http://www.vipbg.vcu.edu
Epistatic interactions are
thought to be important in the etiology of complex traits, especially for
characteristics subject to selection pressure. The detection of epistasis in
linkage studies is relatively straightforward in principle, but suffers from
lack of statistical power. Methods for detecting epistasis in linkage
studies using Mx are presented, and the statistical properties of
likelihood-ratio, bootstrap and permutation tests for it are described.
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Jenae M.
Neiderhiser1. Identifying Sources of Nongenetic Influences on
Change in Parent-Child Relationships from Adolescence to Young Adulthood2.
1Center for
Family Research, Department of Psychiatry and Behavioral Sciences, George
Washington University, Washington, DC USA, 2Supported by NIH
grant MH59014.
Address :
2300 K St., N.W., 3rd Floor Warwick Building, Washington, DC
20037 Telephone: (202) 994-2212 Fax: (202) 994-4812 Email: cfrjmn@gwumc.edu
One of the first studies to
examine genetic and environmental influences on stability and
change in parent-child relationships from adolescence to young adulthood
found that there was only a moderate degree of stability (.28 to .39). In
most cases, this stability was due to shared environmental influences. The
bulk of the change in parent-child relationships through to young adulthood
was also due to environmental factors, although in this case, nonshared
environmental. The current study will attempt to identify the sources of
these nongenetic influences on stability and change in parent-child
relationships. 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. Measures for this study include young adult and parent reports of
current adult child-parent relationship. Potential sources of environmental
influences that will be examined will include parental mental health,
adolescent peer and sibling relationships and current status of romantic
relationship and children in the home that differ for the twin and sibling
pairs.
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Ragnhild B.
Nes, E. Røysamb, K. Tambs & J. R. Harris. Sleep problems and well-being:
Genetic and environmental contributions. Division of Epidemiology, The
Norwegian Institute of Public Health, Oslo, Norway
Address: The Norwegian Institute
of Public Health, Division for Epidemiology, PO Box 4404 Nydalen, 0403 Oslo
Norway Telephone: 47-22042200 Fax: 47-23408247 Email: ragnhild.bang.nes@fhi.no
Sleep problems are common,
affecting health and well-being, risk of accidents, and morbidity. This
study estimates the genetic and environmental contributions to subjectively
reported sleep problems, and investigates the relationship between sleep
disturbance and subjective well-being (SWB) in a cohort of Norwegian twins
born 1967 to 1979. Self report questionnaire data on sleep problems, health
and well-being collected in 1998 from 8,045 twins were analysed using
structural equation modelling to investigate the relative magnitudes of
genetic and environmental influences on phenotypic variance. Furthermore,
sex-specific effects were explored. Preliminary analyses indicate
substantial genetic contributions to the observed variance in sleep
problems. Polychoric correlations were considerably higher in MZ than in DZ
twins for both males (.51 versus .04) and females (.42 versus .15). A
correlation of .15 was observed in the DZ unlike sex group. A model specifying
additive and non-additive genetic effects and individual environmental
effects fit the data best. The phenotypic correlation between sleep
disturbance and SWB was estimated to .40. Cross-twin cross-trait correlation
correlations for each of the five
zygosity by sex groups suggest that genetic factors may contribute
differentially to the association between sleep disturbance and SWB in males
and females. Further analyses of the relationship between reported sleep
problems and SWB will be presented, and results pertaining to sex
differences discussed. Conclusions: Genetic factors contribute
substantially to the variation in reported sleep problems. Moreover,
cross-twin cross-trait correlations indicate sex-specific genetic effects
for sleep problems and SWB
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Lars-Göran Nilsson1,7,
Rolf Adolfsson2, Lars Bäckman3, Marc Cruts4,
Lars Nyberg5, Brent J. Small6, and Christine Van
Broeckoven4. Impairment of Episodic Memory and Word
Fluency in Carriers of the APOEå4 Allele.
1Department
of Psychology, Stockholm University, Sweden, 2Department of
Clinical Sciences, Psychiatry, Umeå University, Sweden, 3Aging
Research Center, Karolinska Institute, Stockholm, Sweden, 4Department
of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,
University of Antwerp, Belgium, 5Department of Psychology,
Umeå University, Sweden, 6School of Aging Studies,
University of South Florida, Tampa, USA, 7Center for Advanced
Study, Norwegian Academy of of Science and Letters, Oslo, Norway.
Address :
Department of Psychology, Stockholm University, 10691 Stockholm, Sweden
Telephone: +46 8 163940 Fax: +46 8 159342 Email: lgn@psychology.su.se
We examined the
effect of the å4 allele of ApolipoproteinE (APOE) in non-demented
individuals in the age range of 35-90 years of age. In a prospective cohort
study we demonstrated a more pronounced å4-related deficit for
participants in the age of 65 years and older in tasks assessing episodic
recall. Somewhat smaller å4-related deficits for these persons were
found in episodic recognition and verbal fluency. No deficits were found in
tasks assessing vocabulary, primary memory and priming. We also demonstrated
that carriers of the å4 allele in the age of 50-60 years performed at
a higher level than non-carriers of this allele in episodic recall tasks,
but not in episodic recognition tasks, nor in tasks assessing semantic
memory, primary memory and priming. Furthermore, we found a dose effect,
such that carriers of two å4 alleles fail more profoundly in
acquiring and recollecting episodic information than carriers of one å4
allele, who in turn fail more than carriers of non-å4
alleles. The pattern of findings observed for older å4 carriers
suggests that these individuals have particular difficulty when the
executive task demands are high. Several factors (e.g., smaller hippocampal
volumes, less effective neural repair mechanisms, preclinical dementia) may
account for these findings. On the basis of the data obtained we argue that
analyses of the effect of specific genes in cognition should be accompanied
by assessment of performance at a specific level, with due attention to the
age of the individual.
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Syuichi Ooki.
Genetic and environmental influences on some habitual behaviors in childhood.
Department of
Health Science, Ishikawa Prefectural Nursing University, Kahoku, Ishikawa,
Japan.
Address :
Department of Health Science, Ishikawa Prefectural Nursing University,
Tsu7-1 Nakanuma, Takamatsu, Kahoku, Ishikawa, 929-1212, Japan
Telephone: 81 76
281 8377 Fax: 81 76 281 8377 Email: sooki@kj8.so-net.ne.jp
The author
conducted this study to estimate the genetic and environmental contribution
to seven habitual behaviors in childhood, namely sleep talking,
half-sleeping, night terrors, nocturnal enuresis, nail biting, stuttering,
and tics. The subjects were 2029 pairs of twins, consisting of two groups.
The first group of subjects consisted of 937 twin pairs of whose mothers
belong to the several maternal associations for the parents of multiples.
The second group of subjects consisted of 1092 twin pairs of the applicants
to the secondary education school attached to the faculty of education of
the University of Tokyo. The twins' mothers had completed a Addressed or
handed questionnaire. With regard to the above mentioned seven traits, they
selected one answer from the choices 'often', 'sometimes' 'never' and
'unknown' for each twin. Genetic analysis was performed as follows. First
the answers were summarized in the form of two patterns of 2 x 2 contingency
table; 'often' and 'sometimes' or >sometimes= and >never= were included in one category. First,
proband-wise concordance rates were calculated according to zygosity and sex
combination. Then, tetrachoric correlations of the contingency table were
calculated using the program package PRELIS2. Furthermore, covariance
structure analysis was performed for several genetic models using the program
package LISREL8. The results were as follows. Univariate genetic analysis
showed that all traits were under genetic control of varying level. Sleep
talking, half-sleeping and night terrors were under strong or moderate
genetic control. As to nocturnal enuresis, the genetic effect was moderate
and shared environmental factors played an important role. Moreover several
traits tended to occur together, and sleep talking, half-sleeping and night
terrors shared common genetic and environmental factors in addition to
specific genetic and environmental factors.
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Maarten W. Peeters1,
Martine A. Thomis1, Hermine H.M. Maes2, Ruth J.F. Loos3,
Albrecht L. Claessens1, Robert Vlietinck4,5, Gaston P.
Beunen1. Causes of stability in explosive
strength during adolescence.
1 Faculty of Physical Education and
Physiotherapy, Katholieke Universiteit Leuven, Belgium, 5 Virginia Institute for
Psychiatric and Behavioral Genetics, Department of Human Genetics, Virginia
Commonwealth University, Richmond, VA, USA, 3 Pennington
Biomedical Research Center, Human Genomics Lab, Baton Rouge, LA, USA, 4
Centre for Human Genetics, Faculty of Medicine, Katholieke Universiteit
Leuven, Belgium, 5 Division of Genetics and Molecular Cell
Biology, Maastricht University, The Netherlands.
Address : Faculteit Lichamelijke Opvoeding en
Kinesitherapie Tervuursevest 101 B-3001 Leuven (Belgium)
Telephone: +32 16329086 Fax: +32 16329197 Email: Maarten.Peeters@flok.kuleuven.ac.be
Tracking or stability of vertical jump
(VTJ), a measure of explosive strength, has been shown to be low to
moderately high during adolescence (R.M.Malina, RQES, 1996, 67
(suppl), 48-57) though some temporary instability is observed due to
differences in tempo and timing of the adolescent growth spurt. Previous
twin studies have reported heritability estimates ranging between .45 and
.93. The aim of the present study was to link these two findings and try to
determine whether the stability of the trait is mainly caused by genes
and/or environment. Subjects are from the Leuven Longitudinal Twin Study
(LLTS) (n=105 pairs, equally divided over five zygosity groups). VTJ data
was aligned on age at peak height velocity (APHV). Simplex models (D.I.
Boomsma and P.C.M. Molenaar, Behav. Genet., 1987, 17, 111-123) were
fitted to the data in a five group analysis. Non Scalar (NS), Specific
Scalar (SS), General Scalar (GS) and models without sex-differences were
tested. Results show that after aligning the data on APHV, the annual
autocorrelations show a clear simplex structure over a 4 year interval. The
most parsimonious model (AIC) was the GS-AE model. Heritability estimates
ranged between 72.2% (95%CI: 58.0-82.7%) and 82.3% (95%CI: 70.8-92.3%) which
is in agreement with values found in the literature. Additive genetic >innovation= variance was 81.3% (95%CI:
70.1-88.4%) for the first measurement occasion, and trough the transmission
paths explained more than 50% of the total variance at all subsequent
observations, with genetic innovation after the first observation never
explaining more than 9.1%. Unique environmental innovation at the first
measurement occasion, which was 18.7% (95%CI=11.6-29.9%) on the other hand
explained less than 4% of the variation at subsequent time points. It thus
can be concluded that the observed stability of explosive strength during
adolescence is mainly caused by a stable genetic influence in boys and
girls.
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Nicole Philip,
Sabine Sigaudy, Anne Moncla. Microdeletion syndromes as a model for
identifying genes involved in behavioral development in humans. The example
of 22q11.3 microdeletion and Smith-Magenis syndromes.
Department of Medical Genetics, Timone Children=s Hospital, Marseille, France
Address: Département de génétique
médicale, Hôpital d=Enfants de la Timone, 13385, Marseille Cedex 5, France Telephone :
04 91 38 66 30. Email : nicole.philip@ap-hm.fr
Microdeletions and
microduplications, not visible by routine chromosome analysis are a major
cause of congenital malformations
and mental retardation in human. Most of these rerarrangements were
described during the last 10 years, as the result of improved cytogenetic
techniques. In most cases, the deletion ranges from 2 to 3Mb and include up
to 30 different genes. A microdeletion syndrome is characterized by specific
but rather subtle clinical manifestations that make the diagnosis easy to
trained clinicians. The presence of
characteristic behavioral traits is another hallmark of many of these
syndromes. We will focus our presentation on two examples and present the
experience of the department of medical genetics of Marseille. Microdeletion
of chromosome 22q11.3 is a rather frequent anomaly, affecting one child out
of 4000. The main clinical manifestations are a subtle facial dysmorphism, congenital
heart defects in 2/3, hypocalcemia, velopharyngeal insufficiency and
learning disabilities. Psychiatric problems, especially schizophrenia occur
in approximately 15% of patients. According to the wide clinical variability
among patients, it is hard to define a single pattern of behavior in 22q11
microdeletion syndromes. Conversely, patients with a Smith-Magenis syndrome
due to a 17p12.2 microdeletion
display a peculiar behavioral phenotype which is characteristic
enough to be a major diagnostic clue. Self-injurious behavior and prominent
sleep disturbances are seen in the majority of patients, but appear to be
age-related.
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Alison Pike1
and Thalia C. Eley2. Relations among Parenting and Extra-familial
Relationships: Nature or Nurture?
1Department
of Psychology, University of Sussex, UK, 2Social, Genetic,
Developmental Psychiatry Centre, Institute of Psychiatry, King=s College London, UK, 3 The Surrey
Adolescent Twin Study was supported by a grant from the University of Surrey
Pro-Vice Chancellor=s Fund to
the first author. The G1219 study
was supported by the W T Grant Foundation and by a Medical Research Council
training fellowship to the second author.
Address :
Psychology Department, University of Sussex, Brighton, BN1 9QH, UK Phone: 44 1273 877288 Fax: 44 1273 678058 Email: alisonp@sussex.ac.uk
By the time
children enter into adolescence, time spent with peers is more than double
that spent with parents (R. W. Larson, M. H. Richards, G. Moneta, G.
Holmbeck, and E. Duckett, 1996, Dev. Psych. 32, 744-754). However, both cross-sectional and
longitudinal associations between parenting and peer group characteristics,
as well as friendship quality, suggest that parents continue to exert
influence (e.g., M. Gold, and D. S. Yanof, 1985, J of Pers. And Soc.
Psych. 49, 654-659). The
current study examined associations between parenting and both peer group
characteristics and friendship quality within two twin samples. The Surrey Adolescent Twin Study consists
of 200 twin pairs aged 12-14 years, and includes parent and child reports of
the parent-child relationships, and adolescent reports of peer group
characteristics and friendship quality.
G1219 consists of over 1100 twin and sibling pairs aged 12-20 years,
and includes adolescent reports of the relationship constructs. Phenotypic analysis revealed that
parenting was moderately associated with peer group characteristics and
friendship quality for the younger twins (aged 12 B 15), but
correlations among the constructs was negligible for the older adolescents
in G1219. Univariate analyses
indicated that both the parent and peer relationship measures are moderately
genetically influenced, and that nonshared environmental factors account for
more of the variance than do shared environmental factors when adolescent
reports are utilized. Replicating
previous research, parent reports of their own parenting indicated similar
treatment of their children (shared environment). Bivariate model-fitting analyses from G1219 indicate that the
covariance between parenting and peer relationships is largely due to common
genetic influence. If replicated
using the Surrey Adolescent Twin Study, such findings suggest that
individual (personality?) traits of children may explain much of the
consistency seen across relationships, and that parenting per se may not
play a vital role in shaping children=s peer
relations.
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Robert Plomin1. Pooled DNA on chips: Genotyping large
samples of cases and controls for thousands of SNPs simultaneously.
1Social
Genetic and Developmental Psychiatry Centre, Institute of Psychiatry,
London, UK. Supported by UK Medical Research Council Program Grant G9424799.
Address :
Social, Genetic
and Developmental Psychiatry Centre, Institute of Psychiatry, King=s College London, Box P080, London, UK SE5
8AF
Telephone: 44 207
848-0893 Fax: 44 207 848-0895 E-mail: rplomin@iop.kcl.ac.uk
Heritability is
ubiquitous for behavioral dimensions and disorders, which means that DNA
differences exist that cause these differences among individuals. However, progress has been slow towards
reliably identifying these DNA differences.
A major reason for this slow progress is inadequate power to detect
small effect sizes. Power to detect
small effects sizes (<1%) requires allelic association rather than
linkage. Rather than examining just
a few genes, allelic association approaches need to be systematic as linkage
studies are. One way to conduct
systematic genome scans with association is to use microarrays (chips) that
simultaneously genotype thousands of single-nucleotide polymorphisms
(SNPs). However, the use of chips
seems incompatible with large samples because each chip costs several
hundred dollars and can be used only once.
The resolution is to use pooled DNA on chips. Since 1996, we have been using pooled DNA
to genotype groups of cases and controls in which a small amount of DNA from
each individual in a group is pooled.
For example, 500 SNPs can be screened for the cost of genotyping one
SNP for 500 cases and 500 controls.
We are now able to use pooled DNA on chips (Affymetrix). We have shown that genotyping pooled DNA
on chips is highly reliable (comparing replicate pools), valid (comparing
pooled results to individual genotyping results) and sensitive to small
allelic frequency differences between cases and controls (using spiked pools
that systematically vary allelic frequency differences). We are currently using pooled DNA on
chips to conduct allelic association genome screens for 10,000 SNPs in genes
(GeneChip7 Mapping 10K Array Xba 131) for 500 cases
and 1000 controls selected from a community sample of 15,000 UK twins. This approach is being applied to several
disorders including reading disability, language disability, mathematics
disability, mild mental retardation, autistic spectrum disorder, and
psychopathy.
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Michael F.
Pogue-Geile1, Raquel E. Gur2, Ruben C. Gur2,
Laura Almasy3, Joel Wood4, Judy Thompson1,
Sarah Tarbox1, and Vishwajit Nimgaonkar4. Executive
functioning and genetic liability to schizophrenia: Preliminary results from a
large-pedigree, multiplex study5.
1Department
of Psychology, University of Pittsburgh USA, 2Department of
Psychiatry, University of Pennsylvania USA, 3Southwest Foundation
for Biomedical Research, 4Department of Psychiatry, University of
Pittsburgh, 5Supported by NIH MH63480
Address :
Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260
USA, Telephone: 412.624.8818; Email: mfpg@pitt.edu
The overall
importance of genetic variation on the etiology of schizophrenia has been
clearly documented for some time.
However, reliably identifying specific genetic polymorphisms that
contribute to this overall risk has been very difficult, presumably because
there are many contributing loci, each with small effect. One strategy that may aid in such
situations is to develop phenotypes that are more sensitive to genetic
liabilities than is the clinical diagnosis itself (i.e., endophenotypes,
Gottesman & Shields, 1972). The
current study employs this approach using neuropsychological phenotypes
within the context of an ongoing linkage study of large pedigrees, multiply
affected with schizophrenia. Here we report preliminary results on the familial
association between the Trails Making Test (TMT), a neuropsychological test
of executive function, and schizophrenia in a subsample of this ongoing
study. The TMT is a timed Aconnect the dot@ test that
involves visual search and working memory.
It has two subtests, TMT-A and TMT-B, with TMT-B having an additional
memory load. If the TMT is sensitive
to genetic liability to schizophrenia, then performance should decrease as
relatives= genetic relatedness to schizophrenia
probands increases. Large families
were ascertained that had at least two relatives diagnosed with
schizophrenia or schizo-affective disorder.
One hundred twelve members from nine families were assessed with the
TMT and diagnosed using the Diagnostic Interview for Genetic Studies
(DIGS). Eighteen probands were
diagnosed with schizophrenia, leaving 94 of their non-schizophrenia
relatives for analysis. Each
relative was assigned a kinship coefficient based on their degree of genetic
relatedness to a schizophrenia proband (e.g., .50 for a sibling, .25 for a
nephew, etc.). Using multiple
regression with age as a covariate, there were significant linear associations
between the time to complete TMT-A and TMT-B and genetic relatedness to
schizophrenia probands (b=.34, p=.001 and b=.27, p=.005). As the genetic relationship to a
schizophrenia proband increased, the time to complete TMT-A and BB also increased, in a linear
fashion. Such results suggest that
the TMT may be sensitive to genetic liability to schizophrenia and thus may
be useful in linkage studies.
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Danielle Posthuma1,
Michelle Luciano2, Eco JC de Geus1,
Margie J Wright2, Nick G Martin2, Dorret I Boomsma1.
Full genome scans for cognition in Dutch and Australian samples.
1Vrije
Universiteit, Amsterdam, The Netherlands; 2Queensland Institute
of Medical Research, Brisbane, Australia. Supported by GenomEUtwin, European
Union Contract No. QLG2-CT-2002-01254,
the Human Frontiers of Science Program (grant number rg0154/1998-B), the
Australian Research Council and the Australian NHMRC=s Program
in Medical Genomics [NHMRC-219178]. Genotyping was carried out by the
Center for Medical Genetics in Marshfield.
Address:
Biological Psychology, Vrije Universiteit, Van der Boechorststraat 1,
1081 BT Amsterdam,
The Netherlands, fax 31-20-4448832, Telephone 31-20-4448814, Email: danielle@psy.vu.nl
Psychometric IQ
was assessed in Dutch and Australian extended twin families. The Dutch
sample consisted of 793 subjects from 317 families, aged between 17 and 68
years. The Australian sample consisted of 1339 subjects from 603 families,
aged between 15 and 22 years. Heritability estimates of psychometric IQ ranged between .80 and .90 in both
samples. On subsamples of the Dutch and Australian samples genotypic marker
data has been collected. Preliminary independent scans in the Australian
sample (762 individuals from 345 families) and Dutch samples (102
individuals from 37 families) suggested linkage for at least one similar
region (lodscores Australian sample > 3, Dutch sample > 1.5) .
Simultaneous scans will be conducted to determine whether these linkage
peaks are actual replications in both samples.
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Carol A. Prescott1,
Jonathan S. Kuhn1 and Nancy L. Pedersen2 . French
Paradox Redux: Are the cardio-protective
effects of moderate alcohol consumption direct or indirect? 3
1 Virginia
Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth
University, Richmond VA USA, 2 Department of Medical
Epidemiology, Karolinska Institutet, Stockholm, Sweden, 3 Supported
by the Swedish Scientific Council, the Swedish Ministry of Higher Education,
and a grant from the U.S. National Institutes of Health (AG08724).
Address :
P.O. Box 980126, Virginia Commonwealth University, Richmond VA 23298 USA Telephone:
(804) 828-5968 Fax: (804)
828-1471 Email: cprescott@vcu.edu
Moderate drinking
has been associated with decreased risk for atherosclerotic cardiovascular
disease (CVD). This effect has been called the AFrench
Paradox@ because of the lower CVD rates in some
regions of France despite a diet high in saturated fat. Several
physiological mechanisms for the protective effects of alcohol have been
proposed, but these do not appear to account completely for the effects
observed. An alternative explanation is that the association is indirect:
moderate drinkers, particularly wine drinkers, engage in health and
lifestyle behaviors which are responsible for the reduced risk for CVD. We
addressed these alternatives using a 30-year follow-up study of participants
from the Swedish Twin Registry born between 1882 and 1958. Over 29,000 twins
who provided data on alcohol consumption and other health and lifestyle
factors in the 1960=s and 1970=s were matched to national hospitalization
and cause of death records to identify morbidity and mortality due to
CVD. The sample includes more than
9,000 deceased individuals with known cause of death (including >4,500
due to CVD), and over 8,900 individuals with hospital admissions associated
with CVD. We examined the
association between level of alcohol consumption and risk for CVD using a
cotwin-control design (comparing CVD outcomes in pairs discordant for level
of alcohol consumption) and a discordant pair design (comparing alcohol
consumption in pairs discordant for CVD outcomes).
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J. Drew Prosser1
and Y.-K. Kim1. Kin recognition in Drosophila paulistorum:
relatedness vs familiarity2.
1Department
of Genetics, University of Georgia, Athens GA USA, 2Partly
supported by CURO Summer Fellowship at UGA
Address :
Department of Genetics, University of Georgia, Athens, GA 30602
Telephone: 706 542
1448, Fax: 706 543910, Email:yongkyu@uga.edu
Kin recognition
serves as an inbreeding avoidance mechanism, which is a key to maintaining
the overall fitness of a species (W. D. Hamilton, 1964, J. Theor. Biol.
7, 1-52; P. Bateson, 1983, in P. Bateson, ed., Mate Choice,
pp. 257-277, Cambridge University, Cambridge). Kim (in press) has
demonstrated that Drosophila paulistorum, when given a choice, prefer
to mate with genetically non-related individuals rather than with siblings.
Further, when siblings or non-siblings were raised together, they had
reduced sexual activities and consequently avoided mating. In an attempt to
further understand kin recognition in D. paulistorum, we have
investigated 1) whether they discriminate between different degrees of
relatedness; and 2) whether they use genetically-determined cues such as
recognition alleles. In female choice situations, one female was placed in
mating chambers with a male sibling and a male half-sibling (HS tests); one
female with a male sibling and a male cousin (C tests); and one female with
a male sibling and a male non-sibling (NS tests), respectively, without
prior experience of either male during development. Current data showed
that there were no significant differences in mate choice between siblings
and individuals of different degrees of relatedness (p=0.1573 for HS;
p=0.3870 for C; p=0.2059 for NS). These results suggest that
1) Drosophila kin recognition is based solely on familiarity acquired
during developmental experience rather than genetic relatedness; 2) they
treat the Afamiliar@ as kin;
3) chemical cues may be involved in this sort of kin recognition; and 4)
familiarity or early association during development leads to avoidance of
interbreeding with siblings.
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Shaun Purcell1,2.
Gene-environment interaction and association analysis.
1Whitehead
Institute, MIT, Cambridge, MA, USA. 2Social, Genetic &
Developmental Psychiatry Research Centre, London, UK.
Address :
Room 463, Daly Lab, Whitehead Institute, MIT, Cambridge, MA, USA.
02142-1479.
Gene-environment
interaction (GxE) (genetic control of sensitivity to the environment, or,
conversely, environmental control of gene effect) is an area of current
focus in complex trait genetics. Consideration of GxE could potentially help
to map genes and elucidate biological pathways. However, as has long been
appreciated in epidemiology, the analysis of interactions is a difficult
area harboring unresolved problems: a central problem when dealing with
quantitative traits is that of scale dependence. Interactions can be induced
or attenuated by transformation of the trait variable. For a botanical
example: the length of a leaf might appear to be additive with respect to a
certain genotype; if, however, one were to measure leaf surface area, one
might conclude dominance effects instead. More subtle effects are to be
expected with polygenic behavioral measures that have no absolute unit of
phenotypic measurement. With these well-known issues in mind, two novel
likelihood-based methods are developed, both of which model genotype
conditional on trait value (which is generally more robust to mild
nonnormality and sample selection). The performance of the likelihood-based
models and two standard regression-based models is compared, in unselected,
selected and trait-transformed samples. One likelihood approach appears to
be the most generally robust. This approach has been extended to nuclear
families, in the software package >cafe=. Furthermore, some interesting
differences in the performance of this likelihood method versus the standard
regression approach hint at the possibility of new, more robust methods.
Finally, a set of simulations performed within a developmental framework is
presented. These simulations show why we should expect to encounter
nonlinear scaling effects in complex behavioral variables. The consequence
of this is that, if naïve statistical methods are applied, we should expect
to see many >statistical=
interactions that do not represent true interaction on any >biological= level.
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Sukumar T. Rao1,
Ming-Ming Zhou1, Robert J. Merker1, Mary A. Mann2,
Gerald D. Fischbach2, Jay A. Gingrich1. Behavioral
alterations in mice with a reduced Neregulin-1 Ig domain isoform.
1Department
of Psychiatry, Columbia University, New York NY USA, 2Center for
Neurobiology and Behavior, Columbia University, New York NY USA.
Address :
1051 Riverside Drive Unit #40, New York, NY 10032
Phone:
212-543-6903 Fax: 212-543-5467 Email: str14@columbia.edu
The Neuregulin-1
(NRG-1) gene has been linked to increased susceptibility for schizophrenia
(H. Stefansson et al., 2002, Am. J. Hum. Genet. 71, 877-92). Our study
examines the behavior of mice with a partially disrupted NRG-1
Immunoglobulin (Ig) domain. This work complements our experiments with NRG-1
Transmembrane (TM) mutants, which showed open field hyperactivity, decreased
prepulse inhibition, and reduced social interaction in relation to their
wild type littermates. As with the TM mutants, our Ig mutant mice
demonstrated significantly increased locomotor activity in an open field
task. However, these mice showed normal prepulse inhibition and normal
performance in motor tasks that tested forelimb grip strength and
the ability to
balance on a rotating rod. In a social interaction task, the Ig mutants
showed deficits in anogenital investigation and a significantly increased
duration of social avoidance. In olfactory discrimination tasks that paired
food rewards with particular odorants, Ig mutants exhibited consistently
longer latencies to food acquisition. The last finding, though still
preliminary, coincides with studies that show a relationship between
olfaction and social drive (D. Malaspina, E. Coleman, 2003, Arch. Gen.
Psychiatry. 60, 578-84). We are also testing the ability of these mice to
discriminate between structurally similar odorant pairs (eg. enantiomers)
that have distinct odors - this experiment will assess sensitivity to minor
structural differences in the olfactory system of the Ig mutant mice. From
our studies thus far, we conclude that Ig mutants display several
endophenotypes consistent with schizophrenia in humans (hyperactivity,
social deficits, olfactory discrimination problems). However, schizophrenic
endophenotypes such as motor deficits and decreased prepulse inhibition
appear to be induced by disruptions in other NRG-1 isoforms.
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Chandra A.
Reynolds1, Jonathan Prince2, Lars Feuk2,
Anthony Brookes2, Margaret Gatz3,4, Nancy
L. Pedersen3,4. The association of three amyloid-related
candidates and longitudinal memory performance in the second half of the
life-span.5
1Department
of Psychology, University of California at Riverside, 2Center for
Genomics and Bioinformatics, Karolinska Institutet, 3Department
of Medical Epidemiology and Biostatistics, Karolinska Institutet 4Department
of Psychology, University of Southern California 5Supported by
NIA Grants AG17561, AG04563, and AG10175.
Relatively
little is known about specific genes involved in memory performance in
nondemented aging populations compared to the multitude of studies on
Alzheimer=s disease. We considered
polymorphisms of the amyloid-related APOE, A2M and LRP genes and
longitudinal memory performance in twins from the Swedish Adoption Twin
Study of Aging (SATSA). Working memory, immediate and delayed recall, and delayed
figural recognition tasks were assessed across four in-person testing (IPT)
sessions spanning 13 years in 798 nondemented twins. Empirical Bayes
estimates of the latent growth parameters for each memory trait served as
outcomes for the association analyses.
Participants at the third IPT were sequenced for APOE, A2M, and LRP
variants. Those with both genotyping and memory scores included 478
individuals from 252 MZ and DZ pairs.
Models examining additive allelic association and dominance
deviations within and between the twin siblings were fit adjusting for age,
sex, and education. For APOE, dominance deviations were significant for the
working memory linear slope (p<.03) as well as for the intercept for the
immediate recall task (p<.01), suggesting that interactions among APOE
alleles were important. Predicted
growth curves indicated lower working memory performance before age 65 but a
less rapid decline for APOE e4 homozygotes compared to those with at least
one copy of the e2 or e3 alleles. Immediate recall performance was lower for
those homozygous for the APOE e4 allele at all ages. The A2M
insertion/deletion variant was associated with the linear rate of change at
age 65 years for the delayed figural recognition task (p=.005) wherein those
homozygous for the rare deletion variant were predicted to exhibit a steeper
linear decline at age 65 years. No significant associations were observed
for the LRP variant. The current findings imply a role for apolipoprotein E
and alpha-2-macroglobulin on longitudinal memory performance in nondemented
older adults.
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Sally-Ann Rhea1,
Brett C. Haberstick1, Robin P. Corley1, and Stacey S.
Cherny2. Friends and Families: A combined twin-adoption analysis
of parenting and peer relationships3.
1Institute
for Behavioral Genetics, University of Colorado, Boulder, CO USA, 2Wellcome
Trust Centre for Human Genetics, University of Oxford, Oxford, UK, 3Supported
by grants HD10333, MH43899 and DA11015c
Address:
Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80304
Telehone: 303 492 2822 Fax: 303 492 8063 Email: rhea@colorado.edu
We have combined
samples and extended the age range from two previously reported analyses of
the relationship among self-rated parenting style, child rated family
environment, and teacher rated adolescent popularity. The adoption study
reported evidence for genetic influence as well as parental influence on
change in popularity (T.G. O'Connor, J.M. Jenkins, J.K. Hewitt, J.C.
DeFries, and R. Plomin, 2001, Marriage and Family Review, 33,
251-271). The twin study found evidence for familial influence but in
contrast to the adoption study, could not distinguish between genetic and
shared environmental influence. Further, it appeared that rather than
parents influencing change in popularity, popularity at the younger age
predicted family variables at the later age (S.A. Rhea, B.C. Haberstick, and
R. Corley, 2003, Behavior Genetics, 33, 715). In this study
combining the Colorado Adoption Project (CAP; n=672) and the Longitudinal
Twin Study (LTS; n=840), we continue to find that self-rated parenting style
is quite stable across the original age range, 10 to12, as well as to age 14
(.61 to .69, p <.01). Both child-rated quality of the family environment
and teacher-rated popularity of the child are also stable but less so (.33
to .45, p < .01 for the child ratings and .35 to .44, p < .01 for the
teacher ratings). And again, popularity as rated by different teachers at
each age in the range appears to influence positive family environment at
the later ages.
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Soo Hyun Rhee1,
2, Erik G. Willcutt1, 2, Christie A. Hartman1, 2,
Bruce F. Pennington3, and John C. DeFries1, 2. Test of
alternative hypotheses explaining the comorbidity between
attention-deficit/hyperactivity disorder and conduct disorder4.
1Department
of Psychology and 2Institute for Behavioral Genetics, University
of Colorado, Boulder, CO USA, 3Department of Psychology,
University of Denver, Denver, CO USA, 4Supported by NIH Grants
DA-13956, HD-27802, MH16880, MH12100, MH38820, and MH04024.
Address :
Institute for Behavioral Genetics Campus Box 447 University of Colorado,
Boulder, CO 80309 Telephone: (303) 492-4631 Fax: (303) 492-8063 Email:
soo.rhee@colorado.edu
There is
significant comorbidity between attention-deficit/hyperactivity disorder
(ADHD) and conduct disorder (CD).
The conclusions of studies that have tested alternative hypotheses
explaining the causes of comorbidity between ADHD and CD have been
conflicting. Researchers who tested
alternative comorbidity models by comparing the prevalences of disorders in
different diagnostic groups concluded that ADHD and CD co-occur because the
comorbid condition (i.e., ADHD+CD) is a distinct, separate subtype (the
three independent disorders model, e.g., S.V. Faraone, J. Biederman, J.G.
Jetton, M.T. Tsuang, 1997, Psychol. Med. 27, 291-300). In contrast, behavior geneticists testing
multivariate models using biometrical model fitting have concluded that
there are substantial common genetic influences on ADHD and CD (the
correlated liabilities model, e.g., T.S. Nadder, J.L. Silberg, L.J. Eaves,
H.H. Maes, J.M. Meyer, 1998, Behav. Genet. 28, 83-99). Given the conflicting conclusions in the
literature, we tested both hypotheses using the same analytical approach in
a twin sample enriched with individuals with ADHD and reading
difficulties. The participants were
110 MZ twin pairs and 182 DZ twin pairs recruited from the Colorado Learning
Disabilities Research Center twin study.
In addition to the three independent disorders model and the
correlated liabilities model, we tested eleven additional comorbidity models
using the Neale and Kendler model fitting approach (M.C. Neale, K.S.
Kendler, 1995, Am. J. Hum. Genet. 57, 935-953) while
correcting for the over-sampling of individuals with ADHD. The three independent disorders model did
not fit the data, whereas the correlated liabilities model fit the data
well. Several other comorbidity
models fit the data as well as or better than the correlated liabilities
model. In conclusion, the results
suggest that shared genetic influences are a better explanation for the
comorbidity between ADHD and CD than the presence of a separate ADHD+CD
subtype.
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Frances
Rice 1 Gordon T Harold 2 and Anita Thapar 1.
The influence of family conflict in predicting childhood and adolescent
depression: differential effects according to familial and genetic risk for
depression.
1
Department of Psychological Medicine, University of Wales College of
Medicine, Cardiff U.K, 2 School of Psychology, Cardiff
University, Cardiff, U.K.
Address :
Department of Psychological Medicine, University of Wales College of
Medicine, Heath Park, Cardiff, CF14 4XN, U.K. Telephone: (+44) (0)29 20
742201 Fax: (+44) (0)2920 74 7839
Email: ricef@cardiff.ac.uk
Exposure to
high levels of unresolved inter-parental conflict has been shown to put
children at an increased risk of a wide range of adjustment problems
including depressive symptoms (E.M. Cummings & P. Davies, 2002, Jl
Child Psychol and Psych 43, 31-63).
However, there is heterogeneity in the outcomes of children exposed
to family conflict (E.M. Cummings and P.J. Davies 1994 J Child Psychol
Psych 35, 73-112). Such
observations of variability in responses to adversity point to the
importance of differential sensitivity to the environment. The factors that influence sensitivity to
environmental stress may involve environmental or biological
mechanisms. In the present study we
examined the hypothesis that familial and genetic risk for depression
moderates the influence of family conflict in predicting depression in young
people. Families from a population-based register of all twin births between
1980 and 1991 in Greater Manchester, U.K were invited to participate. This
register forms a sub-sample of the Cardiff Study of Twins in All-Wales and
North-west England (CASTANET). The Family Environment Scale (R.H. Moos and
B.S. Moos, 1994, Consulting Psychologists Press, CA) was completed by
the parents of 2082 twin pairs aged 5-17 years. Data on depressive symptoms
were collected three years later.
Linear regression analysis was used to assess the impact of family
conflict according to genetic and familial risk for depression. Potential moderation of family conflict
on the genetic and environmental components of variance was assessed using a
moderator model (S. Purcell, 2002 Twin Research 5, 554-571). Results indicated that the influence of
family conflict in predicting depression was greater in those individuals at
familial and genetic risk for depression and that the importance of genetic
and shared environmental (familial) influences on depression was greater as
levels of family conflict increased.
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Frances
Rice 1 and Anita Thapar 1. The effect of birth weight
with genetic susceptibility in predicting childhood and adolescent
depression.
1Department
of Psychological Medicine, University of Wales College of Medicine, Cardiff,
U.K.
Address :
Department of Psychological Medicine, University of Wales College of
Medicine, Heath Park, Cardiff, CF14 4XN, U.K Telephone: (+44) (0)29 20
742201 Fax: (+44) (0)2920 74 7839 Email: ricef@cardiff.ac.uk
Low birth
weight and low birth weight gain has been associated with depression and
related outcomes in adults. It has
thus been suggested that risk for depression may originate in utero and be
mediated through early environmental mechanisms (D.J.P. Barker, 1998, Edinburgh:
Churchill Livingston). However,
depression is also influenced by genes and the effect of environmental
stressors can vary according to genetic and familial susceptibility. The aim of this study, therefore, was to
examine the relationship between birth weight and depression symptoms,
taking into account genetic risk for depression. Families from a population-based register of all twin births
between 1980 and 1991 in Greater Manchester, U.K were invited to
participate. This register forms a sub-sample of the Cardiff Study of Twins
in All-Wales and North-west England (CASTANET). 2046 twins aged 8 to 17 years from 1023 families were included. Data were obtained by parental report and
analysed using regression analysis.
The effect of birth weight adjusted for gestational age, in
influencing depressive symptoms was greater for individuals at genetic or
familial risk for depression. Foetal
growth as indexed by birth weight interacts with genetic risk for depression
in influencing early depression symptoms.
This observation may have public health implications for children who
are small for gestational age and have a family history of depression.
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Joseph Lee Rodgers
and David Bard. Multivariate Models of Fertility Precursors and Outcomes in
the National Longitudinal. Survey of Youth.
Department of
Psychology, University of Oklahoma, Norman OK USA.
Address :
Department of Psychology, 455 W. Lindsey, Norman OK 73019 Telephone: 405-325-4591 Fax: 405-325-4737
e-mail: jrodgers@ou.edu
In past research
we have demonstrated genetic variance related to fertility precursors and
outcomes in several different data sources, including the National
Longitudinal Survey of Youth (NLSY).
These demonstrations have emerged from univariate biometrical models
applied to
pubertal onset, age at first intercourse, intentions/expectations to get
pregnant, first attempt to get pregnant, and family size at several
different ages. In one case, we
developed a bivariate model of the genetic and environmental overlap between
age at first attempt to get pregnant and number of children by age 35, which
showed statistically significant genetic overlap in the variance sources
underlying these phenotypes. In the
current paper, we present several two, three, and four-variable cholesky
models accounting for shared variance among these different fertility
measures. The cholesky model is
appropriate when there are time-related constraints on the fertility
measures B for example, when modeling age at first
intercourse, age at first pregnancy, and age at first birth. The data source is the 6000+ females in
the NLSY79 survey, a household probability sample of 14-21 year old
adolescents in 1979 who have been followed longitudinal since then. The females from that original data
source had given birth to more than 10,000 children by the 2000 data
collection round, and detailed information about the fertility measures
listed above is available for most of those respondents. The biometrical kinship information is
obtained from a kinship linking algorithm developed around ten years ago,
and used successfully in over a dozen biometrical studies of other
phenotypes. Based on past research and on preliminary analyses in
preparation for this paper, we predict more successful and interesting
multivariate biometrical structure underlying the fertility outcomes than
the fertility precursors.
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James
C. Romeis1, 3, Hong Xian2, 3, Andrew C. Heath4
and Nancy Pedersen5. Genetic influences on the
relationship between alcohol dependence, self-reported health and health services
use.
1.Department of Health Mangement and
Policy, School of Public Health, Saint Louis University, St. Louis, MO, USA.
2Research Service, St. Louis VAMC, St. Louis, MO. 3Department
of Medicine, Washington University School of Medicine, Washington University,
Sr. Louis, MO USA. 4Missouri Alcoholism Research Center,
Department of Psychiatry, Washington University School of Medicine,
Washington University, St. Louis, MO USA. 5Department of Medical
Epidemiology and Biostatistics, Karolinska Institutet, SW.
Address: James C. Romeis, Ph.D,
Professor of Health Services Research, Department of Health Mangement and
Policy, School of Public Health , Saint Louis University, St. Louis, MO 63130, USA Telephone 314-977-8148, 314-977-1674
FAX, E-mail:
romeisjc@slu.edu
This study was designed to assess
genetic influences associated with alcohol related problems, self-reported
health [SRH] and health services use [HSU].
The data are taken from the 1996 NIAAA Survey of Alcoholism and
Health Services Use and uses the Vietnam Era Twin [VET] Registry. The
variables are alcohol dependence using DSM III-R criteria, the single item
SRH and the total volume of HSU [inpatient, outpatient and ED] during the
period 1990-1995. SRH is
dichotomized into poor [n=259, 8.84%] and otherwise [n=2667, 91.16%]. HSU is dichotomized as no use [74.94%]
and use. The weighted prevalence of
alcohol dependence is 35.4%. We use
a tri-variate Cholesky to assess the relationship. The results indicate that the heritability of alcohol
dependence [55%] for this sample is within the published range, with a
small, but statistically significant amount of genetic factors associated
with HSU [2%] and SRH [10%]. What is
new is evidence for genetic factors in HSU appear common with SRH. These results indicate that for SRH, 29%
of the variance is genetic factors unique to SRH, 10% is shared with alcohol
dependence and 7% is shared with HSU or a total of 46% of SRH is attributed
to additive genetic factors. The
remainder of variance in SRH is attributed to non-shared environment and
error. While our previous research
indicates there is a heritable relationship between condition, health
behavior and HSU this study indicates there is a heritable relationship
between condition, HSU and SRH.
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Espen Røysamb1,2,
Jennifer R. Harris2, Ted Reichborn-Kjennerud2, and
Kristian Tambs2. Causes of respondent participation and attrition
in questionnaire surveys. A longitudinal twin study.
1 Department of
Psychology, University of Oslo, Norway, 2 Norwegian Institute of
Public Health, Oslo, Norway.
Address : Department of
Psychology, University of Oslo, Pb 1094 Blindern, N-0317 Oslo, Norway
Telephone: + 47 22 84 51 28; Email: espen.roysamb@psykologi.uio.no
The aim is to estimate genetic
and environmental effects on various behaviours related to
survey-responding; participation, reminder-requiring responding, and
attrition over time. Scientific
knowledge regarding the causal factors affecting individual decision making
about survey participation is limited. Method: Invitation to
participate in a questionnaire study was sent to a cohort of 7992 Norwegian
twins in 1992 (T1), and an expanded cohort of 12700 twins in 1998 (T2).
Individual response rates were 74% (T1) and 63% (T2). The total target
sample includes MZ twins and DZ twins of same and opposite sex. Non-respondents were assigned zygosity
based on registry information. Thus, analyses could be performed on the
total cohorts, including both respondents and non-respondents. Phenotypic
survey-related behaviours are subjected to structural equation modelling to
investigate sources of individual differences. In addition, psychological
measures at T1 are investigated in relation to attrition (T1-T2) by means of
multivariate modelling. Results : Polychoric twin-cotwin correlations
for survey participation at T1 were .85 for MZ twins and .71 for DZ twins.
Preliminary analyses indicate both genetic effects, common environmental
effects and non-shared environmental effects on variance in survey
participation. Final results will be presented for estimates of effects on
participation at T1 and T2, and attrition from T1 to T2. Additionally,
associations between psychological measures and attrition will be reported.
Conclusion: Participation B or
nonparticipation B in surveys represents a >hard fact= measure of a
specific behaviour. Our results provide evidence of both genetic and
environmental effects. The role of genes, twin contact, and demographic
factors will be discussed
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Kimberly J.
Saudino1 & Robert Plomin2. Links Between
Hyperactivity and Academic Achievement.
1Psychology
Department, Boston University, Boston, MA USA. 2Social Genetic
and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
Supported by U.S. National Institute of Mental Health Grant R01 MH062375 and
by UK Medical Research Council
Program Grant G9424799.
Address :
Boston University, Department of Psychology, 64 Cummington Street, Boston,
MA 02215 Telephone: 617-353-3679
Fax: 617-353-6933 E-mail:
ksaudino@bu.edu
Hyperactivity in
childhood has been associated with poor academic performance. High activity level in kindergarten and
grade 1 is related to poor reading and mathematics performance both
contemporaneously and at later grades. Although links between hyperactivity
and academic problems are well-documented, the question of the genetic
and/or environmental mechanisms responsible for the association remains
unanswered. The present study explores this question a sample of 1906 twin
pairs (461 MZM, 528 MZF, 445 DZM, 472 DZF; mean age 7.04 years)
participating in the Twins Early Development Study (TEDS). Parents and teachers rated twins= behavior problems on the Strengths and
Difficulties Questionnaire (SDQ).
A general academic achievement score was derived from principal
components analyses of Scholastic Achievement Tests assessing Mathematics
and English. Both parent and teacher
ratings of hyperactivity were significantly correlated with achievement
(parent r = -.31, teacher r=-.43, ps < .001). This association held even after
controlling for the influence of general cognitive ability on achievement
(parent r = -.26, teacher r=-.38, ps < .001). Multivariate model-fitting analyses
revealed significant genetic and nonshared environmental covariance between
the two phenotypes (parent: rg =-.41, re=-.10;
teacher: rg = -.52, re=-.18). For both raters, the sources of
covariance did not significantly differ for males and females. Moreover, the results indicated that the
phenotypic correlations between hyperactivity and achievement were largely
mediated by genetic influences (bivariate heritability parent = .91; bivariate
heritability teacher = .86).
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Jane Scourfield1,
Tom Fowler1, Mendhana Mehta1, Peter McGuffin2.
Why are children taken to see health professionals? Genes play a significant
role3.
1University of
Wales College of Medicine, Cardiff, U.K., 2SGDP research centre,
Institute of Psychiatry, London, U.K., 3Supported by the Medical Research Council, UK.
Address : Dr. Jane
Scourfield, Department of Psychological Medicine, 4th Floor,
University of Wales College of Medicine, Heath Park, Cardiff, CF 14 4XN tel:
029 20743241 fax: 029 20747839 Email: scourfieldj@cardiff.ac.uk
The reasons why 30% of children
with a significant mental disorder are never referred for help have been
understood in the context of sociodemographic influences and the nature of
the child=s problem. This issue has not
previously been examined in a genetically informative sample. This
investigation has examined rates of disorder and of help-seeking in a
population-based sample of twins from the CAStANET study. Logistic
regression analyses showed help-seeking to be significantly associated with
maleness (OR 2.3 (95% CI. = 1.5,
3.6)) and family financial hardship (OR
1.23 (95% C.I.= 1.1, 1.4)). A bivariate cholesky model including psychiatric
caseness and help seeking then showed a significant genetic influence (accounting
for 58% of population variance) on help seeking, which was uncorrelated with
any genetic influence on psychiatric caseness. This suggests that the
presentation of children to health professionals is influenced by genes as
well as social or environmental factors.
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Chizuru
Shikishima1 and Juko Ando2. Genetic and environmental
influences on social attitudes: Evidence for increased shared environmental
effects in families with high cohesion.
1Devision
of Human Relations, Graduate School of Keio University, Mita, Tokyo Japan,
2Faculty of Letters, Keio University, Mita, Tokyo, Japan, 3Supported
by a Grant-in Aid for Scientific Research (A) from the Ministry of
Education, Science, Sports and Culture.
Address :
1-40-30, Naritahigashi, Suginami-ku, Tokyo, 166-0015, Japan
Telephone:
81 3 5307 5722 Fax: 81 3 5307 5722 Email: kana-s@sa2.so-net.ne.jp
To clarify
the genetic and environmental factors which contribute to the resemblance of
social attitudes among members of the Japanese family, data on six
attitudinal dimensions, i.e. authoritarianism, idea-conformity, self-esteem,
citizenship-orientation, conservatism, and ego-centrism, were collected from
164 pairs of monozygotic twins and 96 pairs of dizygotic twins(ages 16-33
years). Univariate model fitting
analyses showed that shared environmental factors explained the familial
resemblance for authoritarianism, idea-conformity, citizenship-orientation,
and ego-centrism, whereas genetic factors explained the familial resemblance
for self-esteem and conservatism.
However, further analyses in which the pairs were divided into two
groups according to the level of cohesion in the family where they were
raised revealed that the familial resemblance in respect to social attitudes
was associated with the cohesion in the family. In authoritarianism and citizenship-orientation, the CE model
was the best fitting model in families with both high and low cohesion, but
the estimate for shared environment was significantly higher in families
with high cohesion. In
idea-conformity and ego-centrism, the best fitting model was the CE model in
families with high cohesion, but the AE model in families with low cohesion.
Furthermore, in self-esteem and conservatism, the ACE model offered the best
explanation in families with high cohesion, while the AE model worked best
in families with low cohesion. In
contrast to these patterns where high family cohesion increases the effect
of shared environment, the difference in parent-offspring verbal
communication did not affect the factors which contribute to the familial
resemblance in social attitudes.
That is, there are some implications that it is not the verbal
relationship but rather the familial affective bonding which contributes to
the transmission of social attitudes in Japanese families, and that an
interaction between the expression of genotype and the family cohesion could
occur as for social attitudes.
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Shelley D. Smith1,
Karen E. Deffenbacher1, R. Boada2, N.
Raitano2, R. Tunick2
, Laurence D.
Shriberg, Richard K. Olson3, Bruce F. Pennington2,
John C. DeFries4. Linkage, association and
candidate-gene analyses for reading disability and speech sound disorder4
1Munroe
Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA, 2Department
of Psychology, University of Denver, Denver, CO, USA, 3Institute
for Behavioral Genetics, University of Colorado, Denver, CO, USA, 4Waisman
Institute, University of Wisconsin, Madison, WI, USA, 5Supported
by NIH grants HD027802 and MH38820.
Address :
985455 Nebraska Medical Center Omaha, NE 68198 USA Telephone: 402 559 5314
Fax: 402 559 4001 Email: ssmith@unmc.edu
We have used
linkage and association analyses to identify and refine chromosomal regions
containing genes influencing specific reading disability (RD). This has been particularly effective in
narrowing the 6p23-21.3 region to several genes within approximately 600 kb.
Mutation analyses in these and other candidate genes are underway, including
a newly described gene on chromosome 15q, ENK1 (Taipale et al., 2003,
Proc Natl Acad Sci U S A. 100,11553-8). As with our previous work (Gayàn
et al., 1999, Am Hum Genet, 64,157-164), linkage and
association results in candidate regions were significant for several
reading-related phenotypes, suggesting that the genes involved have very
basic effects on reading. A history
of speech sound disorder (SSD), an intelligibility disorder of early
childhood, is often reported in children with RD. To determine if this comorbidity is due to common genetic
influences, linkage analysis was performed with SSD phenotypes and markers
from RD candidate regions on chromosomes 1p36, 6p22, and 15q21. Positive linkage results were found in
all three regions using several SSD phenotypes. This supports the hypothesis that RD and SSD share common
deficits, possibly involving phonologic processes.
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Toni N. Smolen1,
Andrew Smolen1 and Erik Willcutt1.
Catechol-O-methyltransferase polymorphism in ADHD2.
1Institute
for Behavioral Genetics, University of Colorado, Boulder, CO USA, 2Supported
by NIH Grants MH 62120 and MH 63941.
Address :
Institute for Behavioral Genetics, UCB 447, University of Colorado, Boulder,
CO 80309 Telephone 303-492-2342 Fax: 303-492-8063 Email: Toni.Smolen@Colorado.edu.
DSM-IV
attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder
consisting of three diagnostic subtypes: inattention, hyperactive-impulsive,
and combined type. Both environmental and genetic factors contribute to the
etiology of this complex disease. In this study we tested the association of
a functional catechol-O-methyl-transferase (COMT; E.C. 2.1.1.6) polymorphism
with ADHD. COMT catalyzes the transfer of a methyl group from
S-adenosylmethionine to catecholamines, including the neurotransmitters
dopamine and norepinephrine, and is one of the major degradative pathways
these neurotransmitters. A G-to-A transition at codon 158/108 (membrane-bound
form/soluble form) of the COMT gene produces a valine-to-methionine
substitution which results in a four-fold reduction (A allele, met enzyme)
in enzyme activity. The study population consisted of 96 probands and 118
matched control subjects (approximately one-half of the target population)
recruited from schools in the Denver, Colorado, USA metropolitan area. The
COMT genotype was measured as a Single Nucleotide Polymorphism using a 5=nucleotidease (Taqman7)
assay. Primers and probes were
obtained from Applied Biosystems (ABI, Foster City, CA) and measured on an
ABI 7000 instrument. The allele and genotype frequencies for Probands were:
59.9% G and 40.1% A; and 36.5% GG, 46.9% AG and 16.7% AA; for controls these were: 51.3% G and 48.7% A; and 28.0% GG, 48.6%
AG and 25.4% AA. There was a marginally significant difference in allele
frequencies (G allele higher in probands) in the predicted direction (p <
.10). Preliminary analyses of ADHD symptom dimensions suggest that this
result may be stronger for DSM-IV inattention than hyperactivity-impulsivity
symptoms (P < .15). These results suggest a possible role of COMT in the
etiology of ADHD in this population.
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Frank M.
Spinath1, Birgit Spinath2, & Robert Plomin3.
Predicting school achievement from intelligence, ability self-perceptions,
and intrinsic values: Phenotypic and genetic analyses in a large twin study
of 9-year-olds.
1University
of Bielefeld, Department of Psychology, Bielefeld, Germany, 2University
of Dortmund, Hochschuldidaktisches Zentrum, Dortmund, Germany. 3Social
Genetic and Developmental Psychiatry Centre, Institute of Psychiatry,
London, UK. TEDS is supported by a programme grant from the UK Medical
Research Council.
Address :
University of Bielefeld, Department of Psychology, PO Box 100131, 33501
Bielefeld, Germany Telephone: 49 521 106-4529 Fax: 49 521 106-6422 E-mail:
fspin@uni-bielefeld.de
Surprisingly
few genetic studies have addressed motivational and other school achievement
related constructs. Possibly, general intelligence (g) is regarded
as such a powerful predictor of academic success that it is questioned
whether other psychological constructs can improve the prediction of
achievement outcomes at all. In the present study, we investigated the
contribution of children=s
domain-specific ability self-perceptions and intrinsic values to the prediction
of school achievement beyond g. Data was available from N = 1,858 twin children
participating in the Twins Early Development Study (TEDS) at age 9. In
addition to our interest in the explanatory power of motivational constructs
over g, our main aims were to study the overall importance of genetic
and environmental influences on ability, motivation, and achievement in a
large community sample of twins, and to study genetic and environmental
contributions to the expected covariance among the variables under study. We
found, that for Mathematics and English, both children=s ability self-perceptions and intrinsic
values contributed significantly to the prediction of achievement compared
to g alone, with ability self-perceptions being the more powerful of
the two motivational constructs. Self-perceived ability and g showed
a moderate correlation which was largely mediated by genetic factors. A
similar result was found when self-perceived ability and achievement were
analyzed. Our results indicate that integrating select motivational
construct into studies of ability and achievement is informative because g
is an important but not the sole predictor of academic success. In addition,
we suggest that studying constructs from the classical realm of educational
psychology might contribute to a fruitful interdisciplinary exchange between
genetic researchers and educational psychologists interested in ability and
school achievement.
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Erica L. Spotts1,
Paul Lichtenstein1. Consistency of adolescent relationship
quality inside and outside the family: a behavior genetic analysis2.
1Karolinska
Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm,
Sweden, 2The Twin Study of Child and Adolescent Development
(TCHAD) s 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 and Biostatistics, Box 281, SE 117-77, Stockholm,
Sweden, Telephone: +468 5248
2351 Fax: +468 31 49 75 E-mail:
Erica.Spotts@meb.ki.se
Many theories predict that
interpersonal styles will similar across relationship type. Often socialization is identified as the
process by which this takes place.
Children learn interaction styles within the family of origin that
are then generalized to extrafamilial relationships such as friendships and
romantic relationships (Roisman, G.I., Masten, A.S., Coatsworth, J.D.,
Tellegen, A., 2004, Child Development, 75, 123-133). However, similarity might also be
accounted for by inherent heritable characteristics that evoke and elicit
similar interpersonal reactions from others (Asendorpf, J.B., A., 2002, In
Vangelisti, A.L., Reis, H.T., & Fitzpatrick, M.A. Stability and
Change in Relationships, 35-56).
This study will use multivariate quantitative genetic analyses to
examine the extent to which genetic and environmental influences account for
overlap among the quality of parent-child, sibling, friend, and romantic
relationships, and whether gender affects the pattern of associations and
influences. Data from the third wave
of the Twin Study of Child and Adolescent Development (TCHAD) in Sweden was
used, when the twins were 16-17 years old.
Measures of parent-child criticism, (child and parent report),
sibling disagreement, and best friend and romantic partner criticism and
affection (all child reports) were assessed. Results suggest that the quality of male relationships is
consistent across all relationship types, whereas female extrafamilial
relationships are relatively unassociated with intrafamilial
relationships. Genetic and shared
environmental influences account for the overlap of relationships, lending
support to theories of socialization, which suggest that interpersonal
interactions are learned in the family of origin, and theories suggesting
that heritable characteristics elicit and evoke particular reactions from
others.
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David S.
Timberlake1, Brett C. Haberstick1, Jeffrey M. Lessem1,
Christian Hopfer2, Andrew Smolen1, Marissa Ehringer1,
and John K. Hewitt1. Heritability of smoking behavior and
associations with dopaminergic polymorphisms in the National Longitudinal
Study of Adolescent Health3.
1Institute
for Behavioral Genetics, University of Colorado, Boulder CO USA, 2Department of Psychiatry,
University of Colorado Health Sciences Center, Denver CO USA, 3Supported
by P01-HD31921, DA000357, HD07289, AA07464, DA11015, EY 012562, and
DA015522. Postdoctoral fellowship funded from NIAAA grant T32 AA07464
(DST).
Address :
Institute for Behavioral Genetics, Campus Box 447 University of Colorado,
Boulder CO 80303 USA. Phone:
303-492-1475 Email:
david.timberlake@colorado.edu
We studied the
genetics of smoking behavior (quantity of cigarettes smoked, age at
initiation, age at regular use) in 2,420 genetic pairs from the National
Longitudinal Study of Adolescent Health assessed on 3 occasions (waves)
during late adolescence and early adulthood. We tested for associations between smoking and three
dopaminergic polymorphisms (DAT1, DRD2, DRD4). Heritability estimates for the quantity of cigarettes smoked/day
at waves 1, 2, and 3 were .64, .67 and .47, respectively. The 9-repeat
allele of the DAT1 polymorphism was significantly associated with smoking
fewer cigarettes at waves 2 (p=.046) and 3 (p=.009). This polymorphism accounted for
approximately 1% of the phenotypic variance, and is hypothesized to alter
dopamine levels that influence the need for nicotine in smokers.
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Sylvie Tordjman1. Towards an
integrated clinico-biological approach to autism.
1CNRS
UMR-7593, Laboratoire Vulnérabilité, Adaptation et Psychopathologie, Hôpital
Pitié-Salpétrière, 47 Boulevard de l=Hôpital,
Paris 75073, France. E-mail : lubart@idf.ext.jussieu.fr
...........
Biological research relevant
to autism has been conducted in very diverse domains (such as
neurochemistry, neuroanatomy and brain imaging, genetics, neuroendocrinology,
or neuroimmunology). The heterogeneity of biological results and the
difficulty of replicating them suggest the existence of autistic subtypes
which may be clinical and/or biological. This presentation reviews
biological research on autism, primarily neuroimaging, biochemical and
genetic studies, and underlines the need to go beyond usual theoretical
boundaries (biological models vs. Psychodynamic theories). In particular,
the place of genetics in an integrated clinico-biological approach to autism
will be discussed taking into account the interactions between pre- or
postnatal environmental factors and the genetic factors studied. Considering
that environmental factors can modify the expression of genes, it is
necessary to study in concert the genetic and the environmental factors in
autism. Furthermore, autism cannot be explained by only one biological cause
but rather involves a multifactorial etiology including biological and
psychological factors. Taking into account this multifactorial etiology, it
is probably through a multidisciplinary approach with the participation of
biologists as well as clinicians that advances will be made. In this regard,
a stress-based clinico-biological model of autism has been developed and
will be discussed. In conclusion, the interest of integrating a biological
approach (information about current progress in biology, close links with
neuropediatrics and biologists, participation in clinical-biological
research) with clinical practices for healthcare teams that work with
autistic children will be emphasized.
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Catherine
Tuvblad1, Martin Grann2, Paul Lichtenstein1.
Low heritability for antisocial behavior among adolescents residing in low
socioeconomic environments3
"
1Department of
Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden, 2The
Centre for Violence Prevention, Karolinska Institutet, Sweden, 3Supported by the Swedish
Council for Working Life and Social Research (project 2001-2368) and the
Swedish Research Council (2001-4231)."
Address: Catherine
Tuvblad, Department of Medical Epidemiology and Biostatistics, Karolinska
Institutet, Box 281, SE-171 77 Stockholm, Sweden, Telephone +46-8-52 48 74 84 Fax
+46-8-31 49 75 E-mail : Catherine.Tuvblad@meb.ki.se
Socioeconomic
status and contextual variables are often assumed to be of importance for
the development of antisocial behavior (ASB), yet they explain only a
fraction of the variance (M. Stouthamer-Loeber, R. Loeber, E. Wei, D.P. Farrington, P.H.
Wikstroem, 2002, J of Consult & Clin Psych, 70: 111-123; R. J. Sampson, S. W. Raudenbush, F. Earls, 1997,
Science, 277: 918-924). An explanation to this paradox could be that
socioeconomic status moderates the influences of genetic and environmental
effects on ASB.
The Twin study of CHild and Adolescent Development (TCHAD) is a Swedish
longitudinal
population-based study including 1,480 twin pairs born 1985-1986. The
present study included 1,139 of the twin pairs, aged 16-17 years. ASB was measured through
self-report. Neighborhood socioeconomic status was assessed using five
variables on aggregated level: ethnicity, educational level, occupational status, buying
power, and neighbourhood crime rate. Family socioeconomic status was assessed by parental reported
educational and occupational status. We used structural equation modeling to
test whether socioeconomic status interacts with latent genetic and
environmental effects of ASB.We found an interaction for girls
between genetic influences and ethnicity; among girls living in a
neighbourhood with a mixed ethnic population, there was little evidence of
genetic effects on ASB, whereas heritability was pronounced in areas with a
high degree of ethnic Swedes. For boys, there was an interaction in parental
reported
occupational status; i.e. low familial occupational status resulted
in less influence of genetic effects on ASB. The results suggest that
adolescents residing in low socioeconomic environments are less sensitive to
genetic influences for ASB.
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Caroline G M. Van Baal1, Meike Bartels1
and Dorret I. Boomsma1. Scholastic achievement and IQ: a moderate
genetic correlation2.
1Department
of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands, 2Supported
by NWO grant 575-5-012
Address :
Vrije Universiteit, Department of Biological Psychology, Van Der
Boechorststraat 1, 1081 BT Amsterdam, The Netherlands Telephone:
+31.20.444.8802 Fax: +31.20.444.8832 Email: gcm.van.baal@psy.vu.nl
Scholastic
achievement, assessed with the Dutch CITO test, is correlated with IQ. This
correlation is mainly genetic (M. Bartels, M.J.H. Rietveld, G.C.M. van Baal,
D.I. Boomsma, 2002, Twin Research, 5, 1-10). Using data of 192
twin pairs, we analyzed specific cognitive abilities, assessed using 12
subtests of the WISC-R, and 4 subtests of the CITO that zoom in on different
aspects of scholastic achievement, such as language related abilities,
ability to tackle mathematical problems, finding/processing of new
information and crystallized knowledge of different scholastic fields (world
orientation). A hierarchical factor analysis of the 12 WISC subtests and the
4 CITO subtests showed 3 first-order genetic AIQ@-factors (Verbal Comprehension, Perceptual
Organization and Freedom of Distractibility) plus 1 first order genetic ACITO@-factor.
These 4 first-order factors all loaded on one second order factor (Ag@). The
genetic CITO factor was moderately influenced by Ag@ but mainly showed influences of a large
genetic factor specific for CITO subtests. Most CITO subtests showed
additional influences of the 3 IQ domains (Verbal Comprehension, Perceptual
Organization and Freedom of Distractibility) that were independent of Ag@. Unique
environmental influences had a moderate impact on all subtests. Common
environmental influences did not show significant influences on WISC
subtests, but accounted for a low to moderate part of the variance of CITO
subtests. However, these environmental influences did not account
substantially to the correlation between subtests of WISC or CITO.
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Toos C.E.M. van Beijsterveldt1
and D.I. Boomsma1. Prevalence, stability, and concordance
rates of gender identification symptoms: A longitudinal study in Dutch twins2.
1Department of Biological
Psychology, Vrije Universiteit, Amsterdam, The Netherlands, 2This
work was supported by NWO Spinoza Grant numbers SPI-56-464 (Boomsma, P.I.)
and by NIMH Grant number MH58799 (Hudziak, P.I.).
Address :
Universiteit, Department of Biological Psychology, van der Boechorststraat
1, 1081 BT Amsterdam, The Netherlands, Telephone: 0031(0)20-4448949 Fax:
0031(0)20-4448832 Email: toos@psy.vu.nl
According the DSM-IV, Gender
Identity Disorder (GID) is characterized by a strong and persistent cross-gender
identification and a persistent discomfort with one=s own sex. It is a rare
syndrome and the onset of cross-gender behaviors and interests can already
start between 2-4 years. Factors involved in the etiology and in the course
of GID are largely unknown: both biological and environmental explanations
have been suggested. In the present study we explore the prevalence,
stability across childhood, and the twin concordance of symptoms of gender
identity. Symptoms of GID were measured using the items: >behaved like the opposite
sex= and >whished to be of the
opposite sex= of the Child Behavior Checklist (CBCL). Maternal CBCL
ratings were obtained at age 7, 10, 12 for respectively about 13000, 8400,
4500 twins as part of an ongoing longitudinal study of the Netherlands Twin
Registry (NTR). At age 7, 3.2% of the boys and 5.2% of the girls sometimes
or frequently behaved like the opposite sex. At age 12, this percentage was
decreased to 1.6% and was similar for boys and girls. About 36% of the
children who behaved like the opposite sex displayed this behavior at age 10
and only 15% did this at age 12. The frequency of the item: >wishes to be of the opposite
sex= was less frequent, but
showed the same sex and developmental pattern as >behaved like the opposite
sex=. At age 7 and 10,
concordance rates for >behaved like the opposite
sex= were higher in MZ than
same-sex DZ twin pairs. However, the concordance rate was also higher in
Opposite Sex DZ twin pairs.
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Stéphanie van den
Berg1, Gonneke Willemsen1, Eco de Geus1,
Dorret Boomsma1. Applying item response theory in
studying latent distributions, sex differences and development in attention
problems2.
1Department of
Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands, 2Supported
by grants from The Netherlands. Organisation for Scientific Research:
NWO 051-02-060, NWO 575-25-006 and NWO 985-10-002.
Address :
Vrije Universiteit Amsterdam, Department of Biological Psychology, Van der
Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands Telephone: +31 (0)20
4448824 Fax: +31 (0)20 4448832 Email: SM.van.den.Berg@psy.vu.nl
Individual scores on
psychological traits are often based on a number of questionnaire items. The
answers to the items (e.g., 0,1,2) are usually summed and these sums are
analysed treating them as continuous and normally distributed traits in the
population. Potential problems with this approach include: 1. non-normal
distribution of sumscores, 2. unclear what is actually measured when the
items differ in indicating the degree of having the trait, 3. the items may
measure an underlying trait that is normally distributed and the skewness of
the observed sumscores might merely reflect a bias in the inclusion of
items, 4. in longitudinal research the inclusion of items may differ across
waves. To address these issues, the IRT approach is introduced and applied
to longitudinal data on attention problems in adulthood, obtained from MZ
and DZ twins and their siblings. Results show that the underlying trait is
normally distributed in both males and females. Scores on the latent trait
were used in a genetic analysis that showed that more than half of the
variance can be accounted for by genetic factors. Individual scores remained
relatively stable over time.
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Stefano
Vicari. Cognitive profiles in
children with Down syndrome
Address :
IRCCS, Ospedale Pediatrico Bambino Gesù, Santa Marinella, Roma, Italy E-mail:
vicari@opbg.net
Intellectual Disabilities (ID)
is a clinical condition characterized by a cognitive deficit that can
present widely differing features. In particular, neuropsychological
research has permitted defining different cognitive profiles among subjects
with ID of different aetiology. For example, important claims have been made
regarding the contrasting profiles of linguistic and cognitive performance
observed in two genetically based syndromes, Williams Syndrome (WS) and Down
Syndrome (DS). Earlier studies suggested a double dissociation, with
language better preserved than non-verbal cognition in children and adults
with WS, and an opposite profile in children and adults with DS. More recent
studies show that this initial characterization was too simple, and that
qualitatively different patterns of deficit observed within both language
and visual-spatial cognition, in both groups. The goal of our presentation
is to present and discuss more detailed data on language, memory and
cognition in a large sample of Italian speakers with DS. Our intent is to
contribute to a more precise definition of the neuropsychological profile of
DS and, in particular, to investigate whether children with DS show a stable
neuropsychological profile with a clear dissociation between visual-spatial
and linguistic abilities, or rather, whether they show atypical profiles
with peaks and valleys both in the cognitive as well in the linguistic
domain. Moreover we are interested in clarifying the relationships among
linguistic and nonlinguistic measures, across life span, to obtain a deeper
understanding of developmental effects and variations in developmental
trajectories. Possible neural substrates for these profiles and trajectories
will be discussed.
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Stefano Vicari,
MD. Neuropsychological profiles of children bearing genetic diseases
(Williams and Down syndromes).
IRCCS, Ospedale
Pediatrico Bambino Gesù, Santa Marinella, Roma, Italy.
E-mail: vicari@opbg.net
Intellectual Disabilities (ID)
is a clinical condition characterized by a cognitive deficit that can
present widely differing features. In particular, neuropsychological
research has permitted defining different cognitive profiles among subjects
with ID of different aetiology. For example, important claims have been made
regarding the contrasting profiles of linguistic and cognitive performance
observed in two genetically based syndromes, Williams Syndrome (WS) and Down
Syndrome (DS). Earlier studies
suggested a double dissociation, with language better preserved than
non-verbal cognition in children and adults with WS, and an opposite profile
in children and adults with DS. More recent studies show that this initial
characterization was too simple, and that qualitatively different patterns
of deficit observed within both language and visual-spatial cognition, in
both groups. The goal of our presentation is to present and discuss more detailed
data on language and cognition in a large sample of Italian speakers with WS
and with DS, results of a cooperative study started in 1995. Our intent is
to contribute to a more precise definition of the neuropsychological profile
of WS and DS and, in particular, to investigate whether children with WS
show a stable neuropsychological profile with a clear dissociation between
visual-spatial and linguistic abilities, or rather, whether they show
atypical profiles with peaks and valleys both in the cognitive as well in
the linguistic domain. Moreover we are interested in clarifying the
relationships among linguistic and nonlinguistic measures, across life span,
to obtain a deeper understanding of developmental effects and variations in developmental
trajectories.
Possible neural substrates for these profiles and trajectories will be
discussed.
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Richard J. Viken1,
Danielle M. Dick,2Jaakko Kaprio3, Lea Pulkkinen4,
& Richard J. Rose1. Genetic and Environmental Influences on
Global Self-Esteem in Adolescent Twins5.
1 Indiana
University, Bloomington, IN USA, 2 Washington University, St.
Louis, MO USA, 3University of Helsinki, Finland, 4University
of Jyväskylä, Finland, 5The Finnish Twin Studies are supported by
AA09203 and AA12502 the NIAAA and by the Academy of Finland.
Address : Department of Psychology Indiana
University 1101 E. 10th Street Bloomington, IN 47405
Telephone: 812-855-1697 Fax: 812-855-4691 E-mail: viken@indiana.edu
The construct of
global self-esteem has played an important role in many popular theories of
behavioral development. Self-esteem
has been considered to have an important causal role in outcomes as varied
as academic achievement, delinquency, substance abuse, occupational
adjustment, and psychiatric disorder.
Increased self-esteem, itself, has been treated as an important
outcome from skilled parenting, as well as from successful educational and
psychological interventions. We investigated genetic and environmental
influences on the Rosenberg global self-esteem scale in 1300 pairs of
14-year-old Finnish twins. We found
significant genetic effects on self-esteem at age 14, with girls showing
evidence of modest shared environmental effects as well. Either female-specific shared
environmental effects or sex-specific genetic effects were required to
account for the reduced opposite sex DZ correlations relative to same-sex DZ
correlations. Twin correlations for
both MZ and DZ twins in the present sample were higher than in previous
studies of global self-esteem in adults and adolescents. Further analyses will investigate the
covariation between global self-esteem and other behavioral measures in
adolescence.
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Alice P. Villatoro1,
Laura A. Baker2, and Adrian Raine3. The questionable
truth of childhood aggression: The effects of child IQ and parental
monitoring on parent-child agreement.4
1, 2, 3 Department
of Psychology, University of Southern California, Los Angeles, CA USA, 4
Supported by NIMH #MH58354
Address :
University Park Campus SGM 501, Los Angeles, CA 90089 USA Telephone: 213 740
2259 Fax: 213 746 9082 E-mail: avillato@usc.edu
The effects of child IQ and
parental monitoring on interrater agreement between the parent and child
reports of the child=s aggression were examined in an
ongoing twin study of childhood behavior problems. The participants included
942 preadolescent (9-10 year old) male and female twins and their primary
caregivers (91.4% biological mothers). Agreement was examined as a function
of various levels of parental monitoring (e.g. the child=s willingness
to disclose information to their parent and the parent=s knowledge
about the child=s whereabouts, activities, and
associations), as well as levels of child IQ. Parent-child agreement across
different levels of rater characteristics was calculated in two ways: first,
by examining correlations between the parent and child ratings; second,
through comparisons of parent and child rated mean levels of aggression.
Results of correlation comparisons showed that both the child=s IQ and the
level of parental monitoring influenced parent-child agreement. In
comparisons of mean levels of aggression, parents rated both boys and girls
higher on aggression than the children rated themselves. Sex-differences in
average aggression ratings were also observed with boys being rated as more
aggressive than girls, both for the parent and child self-reports. Mean
differences between parent and child rated aggression varied across both the
level of child IQ and levels of parental monitoring. These results indicated
that aggression ratings and interrater agreement depend upon characteristics
of the rater reporting the behavior. Currently, investigations are underway
to examine twin concordance in their agreement with their caregivers.
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Sally J. Wadsworth1
and John C. DeFries1. Genetic influences on Reading
Disability as a Function of Gender2
1Institute
for Behavioral Genetics, University of Colorado, Boulder CO, USA, 2Supported by NICHD Center
Grant HD-27802.
Address :
Institute for Behavioral Genetics, University of Colorado, 447 UCB, Boulder
CO 80309-0447 Telephone: 303 492 6795
Fax: 303 492 8063 Email: Sally.Wadsworth@Colorado.EDU
Although it has
been suggested that genetic influences on reading difficulties may differ
between boys and girls, previous DeFries-Fulker regression analyses (DF;
J.C. DeFries and D.W. Fulker, 1985, Beh. Genet., 15,
467-473) of data from same-sex twin pairs
participating in the Colorado Learning Disabilities Research Center (CLDRC)
suggested that the heritability of reading disability (RD) does not differ
as a function of gender (S.J. Wadsworth, V.S. Knopik and J.C. DeFries, 2000,
Reading & Writing: An Interdiscipl. J., 13,
133-145). However, recent
model-fitting analyses of data from both same-sex and opposite-sex pairs
participating in the Twins Early Development Study (TEDS; N. Harlaar, F.M.
Spinath, P.S. Dale and R. Plomin, in press, Journal?) indicated
higher heritability among boys with reading difficulties. Because the
current sample in the CLDRC is substantially larger than that previously
analyzed for gender differences, this hypothesis was tested more rigorously
using data from both same-sex and opposite-sex pairs in this augmented
sample. Composite reading scores (Reading Recognition, Reading Comprehension
and Spelling) from 262 pairs of MZ twins (127 male, 135 female pairs), 214
pairs of same-sex DZ twins (121 male, 93 female), and 156 pairs of
opposite-sex DZ twins were subjected to DF analysis using a model-fitting
approach (S. Purcell and P.C. Sham, 2003, Beh. Genet., 33,
271-278). Results of analysis of
data from male and female twins combined indicated a heritability of .58 for
RD in the full sample. When this
model was extended to test for gender differences in the magnitude of
genetic influences on RD, estimates of h2g were .53
for males and .66 for females, a nonsignificant difference (p >
.3). A test for sex-specific effects
was also nonsignificant. Possible
reasons for the different results between studies, including possible
developmental differences, will be addressed.
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Irwin D. Waldman1.
Criteria for the selection of endophenotypes for candidate gene studies:
Application to executive functions and ADHD.
1 Emory
University, Atlanta, Georgia USA.
Address : Department of Psychology 532 N. Kilgo
Circle Emory University, Atlanta, GA
30322 Telephone: 404-727-7430,
Fax: 404-727-0372 Email: psyiw@emory.edu
There is renewed
interest in the recent psychiatric genetics literature in endophenotypes,
constructs that are posited to be more directly and strongly influenced by
relevant candidate genes than are the manifest symptoms of the psychiatric
disorders that those genes are also thought to underlie. A number of
psychiatric genetics researchers have proposed criteria for the selection of
endophenotypes that might be useful in finding genes that underlie
psychiatric disorders and their symptoms.
These criteria include: 1.the endophenotype has good psychometric
properties, 2. the endophenotype is related to the disorder and its symptoms
in the general population, 3. the endophenotype is expressed regardless of
whether the disorder is present, 4. the endophenotype is expressed at a
higher rate in the unaffected relatives of probands than in randomly
selected individuals from the general population, 5. the endophenotype and
disorder are associated within families (i.e., they Aco-segregate@), 6. the endophenotype is heritable, 7.
there are common genetic influences underlying the endophenotype and the
disorder, 8. the endophenotype must show association and/or linkage with one
(or more) of the candidate genes or genetic loci that underlie the disorder,
and 9. the endophenotype must mediate association and/or linkage
between the candidate gene and the disorder, meaning that the effects of a
particular gene or locus on a disorder are expressed B either in
full or in part B through
the endophenotype. In this paper, I
review some of the analyses that may be used to evaluate the validity and
utility of putative endophenotype measures consistent with these proposed
criteria. I illustrate the use of
such analyses to evaluate putative endophenotypes with data on childhood
ADHD and executive function measures.
To address these issues, I analyze data on ADHD symptoms and
diagnoses and omission and commission errors from a Continuous Performance
Test from both a candidate gene study of clinically-referred children with
ADHD and a study of non-referred twins.
I demonstrate that while both putative endophenotype measures showed
association with several candidate genes in the dopamine system, and met
many of the criteria proposed for their validity and utility, they did not
meet all of the criteria and might have been rejected for use as
endophenotypes in molecular genetic studies on that basis. I conclude with some considerations
regarding the criteria proposed for the selection of endophenotypes and
their use in molecular genetic studies of psychopathology.
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Mary Waldron1H, Andrew C. Heath1,
Eric Turkheimer2, Robert E. Emery2 & Nicholas G.
Martin3. Age at first sexual intercourse and teenage pregnancy.
1Washington
University, St. Louis, MO USA, 2University of Virginia,
Charlottesville, VA USA, 3Queensland Institute of Medical
Research, Brisbane, Australia, H Supported by
T32AA from NIAAA
Address :
Washington University School of Medicine Department of Psychiatry
40 N.
Kingshighway, Suite One St. Louis, MO
63108 USA Telephone:
314-286-0093 Fax:
314-286-2213 E-mail: maryw@matlock.wust.edu
Rates of teenage pregnancy
are higher among adolescents who report first sexual intercourse by age 14
or 15 (J. Manlove, E. Terry, L. Gitelson, A.R. Papillo, and S. Russell,
2000, Family Planning Perspectives, 32, 166-175). Compared to
adolescents reporting an older age at first sexual intercourse, younger
sexually-active adolescents are less effective and less consistent in their
use of contraceptives and as a consequence at increased risk for unintended
pregnancy (D. Glei, 1999, Family Planning Perspectives, 31,
73-80; J. Manlove, S. Ryan, and K. Franzetta, 2003, Perspectives on
Sexual and Reproductive Heath, 35, 246-255). While older age at first sexual
intercourse predicts more consistent and effective contraceptive use, debate
continues regarding the causal role of age at first sexual intercourse and
teenage childbearing risk (K. Luker, 1996, Dubious Conceptions: The Myth
of Teenage Pregnancy, Harvard University Press, Boston, MA). In this report, we examine the hypothesis
that common genetic factors predispose some adolescents to both early sexual
intercourse and teenage pregnancy using data on 2700 female twin pairs drawn
from two cohorts recruited from the Australian Twin Registry. For both older and younger cohorts (born
before or on/after 1964, respectively), results from univariate and
bivariate genetic analyses suggest substantial heritable variation in
teenage pregnancy that is also shared with heritable variation in age at
first intercourse. Results from
two-stage bivariate genetic models that condition teenage pregnancy on
adolescent sexual activity defined as a multiple category variable (virgin,
early age at first sex and late/later age at first sex) are also presented.
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Mary Waldron1H, Andrew C. Heath1,
Eric Turkheimer2, Robert E. Emery2 & Nicholas G.
Martin3. Childhood
adversity and risk for teenage pregnancy:
Examination of gene-environment interplay.
1Washington
University, St. Louis, MO, USA, 2University of Virginia,
Charlottesville, VA, USA, 3Queensland
Institute of Medical Research, Brisbane, Australia, H Supported by
T32AA from NIAAA
Address :
Washington University School of Medicine, Department of Psychiatry
40 N.
Kingshighway, Suite One, St. Louis, MO
63108 USA Telephone:
314-286-0093 Fax:
314-286-2213 E-mail:
maryw@matlock.wust.edu
Rates of teenage
pregnancy are disproportionately high for adolescents from single-parent
families (S. McLanahan and L. Bumpass, 1998, American Journal of Sociology,
94, 130-152), especially those of lower versus higher socioeconomic status
(M.D. Hayward, W.R. Grady, and J.O.G. Billy, 1992, Social Science
Quarterly, 73, 750-772; C. Robbins, H.B. Kaplan, and S.S. Martin, 1985, Journal
of Marriage and the Family, 47, 567-583), and adolescents with sexual
trauma and abuse histories (K. Fiscellla, H.J. Kitzman, R.E. Cole, K.J.
Sidora, and D. Olds, 1998, American Journal of Pediatrics, 101,
620-624). Despite research documenting consistent links between early
adversity and risk for teenage pregnancy, little is known regarding
mechanisms underlying these associations (K. Luker, 1996, Dubious
Conceptions: The Myth of Teenage Pregnancy, Harvard University Press,
Boston, MA). Using data on 2700 female twin pairs drawn from two cohorts
recruited from the Australian Twin Registry, we examine the hypothesis that
genetic influences contribute to risk for teenage pregnancy and further,
that childhood adversity (early trauma/abuse, family SES, parental
separation/divorce) may work to moderate observed heritabilities. Results
from univariate genetic analyses indicate substantial heritable variation in
teenage pregnancy. For both older and younger cohorts (born before or
on/after 1964, respectively), genetic factors account for nearly 50% of
total variation in teenage pregnancy, with shared environment explaining
between 10-15%. When genetic and environmental variance are estimated
conditional upon a continuous measure of childhood adversity,
heritability-by-adversity effects are observed. For twins raised in homes
characterized by relatively little adversity, genetic influences are
substantial. For twins raised in
homes characterized by greater adversity, genetic influences are much
smaller.
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Sandra Wilkniss1,
Eric Turkheimer1, Carol Manning2, Irving Gottesman1,
Lora Baum3, Susan Jones3 , Susan Miesfeldt3.
Communicating Cancer Risk Information in Genetic Counseling: Does Format of Presentation Affect
Understanding?
1Department of Psychology,
University of Virginia, Charlottesville, VA USA, 2Department of
Neurology, University of Virginia Health Sciences Center, Charlottesville,
VA USA, 3Cancer Center Genetics Clinic, University of Virginia,
Charolottesville, VA USA.
Address: Sandra Wilkniss,
PhD, Assistant Professor, Dept. of Psychiatry (M/C 913), U. of Illinois at
Chicago, Chicago IL 60612 Telephone: 917-208-7208 Email: s_wilkniss@hotmail.com
Personal risk for developing
cancer is consistently overestimated by a majority of people at risk for
hereditary adult-onset cancer such as breast-ovarian cancer. Though genetic counseling improves
understanding of benefits and limitations of predictive genetic testing,
knowledge of cancer genetics, and reduces cancer-specific anxiety, it has
failed to significantly improve comprehension of quantitative risk (C.E.
Lerman et al., 1995, J Nat=l Cncr Inst., 87(4),
286-292; C.E. Lerman et al.,1997, Prev Med, 26, S65-S69; S. Lloyd, et
al.,1996, British J Cncr, 74, 482-487).
Recent findings in reasoning under uncertainty suggest that people
reason significantly better using quantitative risk information presented in
natural sampling frequencies rather than probabilities (G. Gigerenzer &
U. Hoffrage, 1995, Psych Rev, 102(4), 684-704; G. Gigerenzer & U.
Hoffrage, 1998, Acad Med, 73(5), 538-540).
In two experiments, we tested the hypotheses that risk comprehension
would improve significantly when quantitative risk values are presented in
natural sampling frequencies (frequency format) compared with probabilities
(probability format) and that improved comprehension would lead to
meaningful changes in test behavior with change in risk status. Experiment 1 tested these hypotheses in
42 patients deciding whether to undergo predictive genetic testing for breast-ovarian
(BRCA1) or colon cancer (HNPCC).
Experiment 2 tested the same hypotheses in a sample of 126 college
undergraduates who believed they were deciding whether to elect predictive
genetic testing for a Acancer susceptibility gene.@ Results supported the hypothesis that risk comprehension was
significantly better in the frequency format condition than in the
probability format condition in both samples. Intention to test differed significantly as a function of risk
but not as a function of presentation format. In addition, significant differences in personal perceived
risk were found across experiments as a function of problem solving ability.
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Erik G. Willcutt1,2,
Bruce F. Pennington3, Richard K. Olson1,2, and John C.
DeFries1. Understanding comorbidity: a twin study of reading
disability and attention-deficit/hyperactivity disorder4.
1Institute
for Behavioral Genetics, University of Colorado, Boulder CO, USA, 2Department
of Psychology, University of Colorado, Boulder CO, USA, 3Department
of Psychology, University of Denver, Denver CO, USA, 4Supported
by NICHD Center Grant HD-27802.
Address :
Department of Psychology, University of Colorado, 345 UCB, Boulder CO 80309.
Telephone: 303 492 3304 Fax: 303
492 2967 Email:
willcutt@psych.colorado.edu
Reading disability
(RD) and attention-deficit/hyperactivity disorder (ADHD) co-occur significantly
more frequently than expected by chance, but the etiology of this
comorbidity is unknown. To test the etiology of RD, ADHD, and their
comorbidity, we conducted univariate and bivariate multiple regression
analyses of data from twin pairs participating in the Colorado Learning
Disabilities Research Center twin study. Same-sex twin pairs were selected
if at least one member of the pair exhibited significant reading
difficulties (99 monozygotic and 80 dizygotic pairs) or symptoms of DSM-IV
attention-deficit/hyperactivity disorder (ADHD; 83 monozygotic and 78
dizygotic pairs). Univariate DeFries-Fulker regression analyses revealed
moderate to high heritability for all measures of reading difficulty and
ADHD (h2g = .59 - .93). Subsequent bivariate analyses
indicated that the relation between reading difficulties and inattention
symptoms is primarily attributable to common genetic influences, whereas
bivariate heritability estimates were not significant for
hyperactivity-impulsivity and any of the reading measures. Reading
difficulties and ADHD symptoms were more highly heritable if the proband met
criteria for both disorders versus RD or ADHD alone, suggesting that future
linkage and association analyses of comorbid RD+ADHD may facilitate the
identification of susceptibility genes for RD, ADHD, and their comorbidity.
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Heike Wolf1,
Peter Borkenau2, Alois Angleitner3, Rainer Riemann1
& Frank M. Spinath3. Multi-method assessment of
personality: An observational study of adult twins.
1
Friedrich-Schiller-University Jena, Germany, 2
Martin-Luther-University Halle, Germany. 3 University of
Bielefeld, Germany. GOSAT was supported by the Deutsche
Forschungsgemeinschaft (DFG).
Address :
Friedrich-Schiller-University Jena, Institute of Psychology, Humboldt=s. 26, 07743
Jena, Germany Telephone: ++49 (0) 3641 945163, Fax: ++49 (0) 3641 945162,
Email: heike.wolf@uni-jena.de
Behavioral
genetic studies on personality clearly indicate that genes account for a
considerable part of individual differences. However, most of these studies
are based on self-reports alone and only few studies incorporate data from
peer ratings or behavior observations. As part of the German Observational
Study of Adult Twins (GOSAT), videotaped behavior of 300 twin pairs in 15
situations was observed in detail by independent judges. Additionally,
prototypicality ratings in terms of the Five-Factor model of personality
were collected for the behavioral categories used for the observations.
This procedure
allowed behavioral genetic analyses on different levels of aggregation. For
the present analyses, we aggregated the detailed behavioral categories first
within each situation and second across different situations. In correspondence with
earlier findings from observational research, genetic and shared
environmental effects on specific behaviors observed in specific situations
tended to be very small. However, on the level of multiple-act criteria more
substantial genetic influence was found. Results of the detailed behavior
observations were compared to personality ratings based on ratings of the
same video material and also to self- and peer reports of personality. The
findings will be discussed within the context of an often proposed
top-down-model of genetic and environmental influences on personality.
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Margie J.
Wright1, Michelle Luciano1, Narelle K. Hansell1,
Gina M. Geffen2 and Nick G. Martin1. A genomic wide
screen of the P3(00) ERP component:
preliminary findings3.
1Queensland
Institute of Medical Research, Brisbane, Australia, 2School of
Psychology, University of Queensland, Brisbane, Australia, 3Collection
of phenotypes was supported by the Australian Research Council and the Human
Frontiers Science Program. The genome scans were supported by the Australian
NHMRC=s Program in Medical Genomics.
Address : Queensland Institute
of Medical Research, PO Royal Brisbane Hospital, Brisbane QLD 4029
Australia. Telephone: (617) 3362 0225
Fax: (617) 3362 0101 Email:
margieW@qimr.edu.au
The P3(00)
event-related potential (ERP) is commonly used as an index of processing
capacity (P3 amplitude) and stimulus evaluation (P3 latency), and in various
clinical groups has been proposed as a phenotypic marker of disease (eg.
Alcoholism, Schizophrenia). In a
sample of adolescent twins we found both P3 amplitude and latency to be
moderately heritable (M.J. Wright et al., 2001, Behav. Genet. 31,
555-565). A genome-wide linkage scan
of 400-761 autosomal markers, at an average spacing of 5-10cM, has now been
completed in 647 twins/siblings (311 families mostly comprising a DZ twin
pair), for whom P3 amplitude and latency data are available. Multipoint linkage analysis using
variance components analysis in Mx was performed on P3 amplitude and P3
latency, measured at frontal, central and parietal electrode sites. Suggestive linkage for P3 amplitude on
chromosomes 6 (parietal sites) and 8 (central sites) was indicated. Linkage results for P3 latency were
somewhat more striking with suggestive linkage found on chromosomes 3, 6 and
11 for P3 latency at parietal sites, chromosomes 4 and 10 for central sites,
and chromosome 9 for frontal sites.
Using a multivariate linkage analysis the results generally indicated
the same chromosomal loci as the univariate findings with only the strength
of the signals varying. These QTL
analyses suggest that several regions of the human genome contain genetic
loci related to the generation of the P3 ERP component, which may be
possible candidate loci for information (cognitive) processing.
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Shinji Yamagata1,
Atsunobu Suzuki1, Kimio Yoshimura2, Nobuhiko Kijima3,
Yutaka Ono4, Juko Ando5. The genetic and environmental
structure of the NEO-PI-R: Facet-level analysis.6
1Department
of Cognitive and Behavioral Sciences, The University of Tokyo, Komaba Tokyo,
Japan, 2Cancer Information and Epidemiology Division, National
Cancer Center Research Institute, Tsukiji Tokyo Japan, 3Psychological
Laboratory, Keio University, Hiyoshi Kanagawa Japan, 4Health
Center, Keio University, Yokohama Kanagawa Japan, 5Faculty of
Letters, Keio University, Mita Tokyo Japan, 6Supported by a
Grant-in Aid for Scientific Research (A) from the Ministry of Education,
Science, Sports and Culture
Address :
Department of Cognitive and Behavioral Sciences, The University of Tokyo,
3-8-1, Komaba, Meguroku, Tokyo, 153-8902, Japan
Telephone: 81 3
5454 6896 Fax: 81 3 5454 6979 Email: yamagata@bayes.c.u-tokyo.ac.jp
Ono et al. (2000, Keio
Journal of Medicine, 49, 152-158) examined the genetic structure
of the NEO Personality Inventory-Revised (NEO-PI-R) and found that five
domains were genetically correlated with each other and at least one common
genetic factor was necessary to explain genetic covariance among them. The current study extended Ono et al.=s study by examining the genetic and
environmental structure of the NEO-PI-R at the facet level. 751 pairs (428 pairs of MZs, 145 pairs of
same sex DZ, 78 pairs of opposite sex DZs) of Japanese twins participated in
this study. Univariate genetic
analyses showed that AE model fit for all of the domains and for most of the
facets. Genetic factor analysis
yielded 5-factor solution, whereas environmental factor analysis yielded
4-factor solution. The genetic
factors almost corresponded to the phenotypic domains, but there were some
facets loading on a couple of factors.
The results suggested the existence of 5 orthogonal genetic factors
underlying human personality, but they may not be exactly same as the
original NEO-PI-R domains.
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