Human Molecular Genetics Advance Access published online on September 6, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh239
© 2004 by Oxford University Press
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1 MRC Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK
* To whom correspondence should be addressed. E-mail: i.craig{at}iop.kcl.ac.uk.
There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (GENESiS: Genetic Environmental-Nature of Emotionality States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n=34,371), using four well validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2,658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller - but statistically powerful - sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64cM (43-70cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47cM (34-63cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.
Article
Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships
2 MRC Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK; Whitehead Institute, Center for Genome Research, Cambridge, Massachusetts, USA
3 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
4 Center for Statistical Genetics, University of Michigan, Ann Arbor, USA
5 Section of Epidemiology, Institute of Psychiatry, King's College, London, UK
6 Department of Psychology, Institute of Psychiatry, King's College, London, UK
7 MRC Social, Genetic, and Developmental Psychiatry Research Centre, Box P080, Institute of Psychiatry, De Crespigny Park, King's College, London SE5 8AF, UK
8 MRC Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK; Department of Psychiatry and Genome Research Centre, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China
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