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Estimating the heritability of reporting stressful life events captured by common genetic variants

Published online by Cambridge University Press:  14 December 2012

R. A. Power*
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
T. Wingenbach
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
S. Cohen-Woods
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
R. Uher
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
M. Y. Ng
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
A. W. Butler
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region, China
M. Ising
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
N. Craddock
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, UK
M. J. Owen
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, UK
A. Korszun
Affiliation:
Barts and The London Medical School, Queen Mary University of London, UK
L. Jones
Affiliation:
Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, UK
I. Jones
Affiliation:
Barts and The London Medical School, Queen Mary University of London, UK
M. Gill
Affiliation:
Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland
J. P. Rice
Affiliation:
Department of Psychiatry, Washington University, St Louis, MO, USA
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Germany
A. Zobel
Affiliation:
Department of Psychiatry, University of Bonn, Germany
O. Mors
Affiliation:
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
A. Placentino
Affiliation:
Psychiatric Unit 23, Department of Mental Health, Spedali Civili Hospital and Biological Psychiatry Unit, Centro San Giovanni di Dio, FBF, Brescia, Italy
M. Rietschel
Affiliation:
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
S. Lucae
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
F. Holsboer
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
E. B. Binder
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
R. Keers
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK Barts and The London Medical School, Queen Mary University of London, UK
F. Tozzi
Affiliation:
GlaxoSmithKline Research and Development, Verona, Italy
P. Muglia
Affiliation:
GlaxoSmithKline Research and Development, Verona, Italy Department of Psychiatry, University of Toronto, Canada NeuroSearch A/S, Ballerup, Denmark
G. Breen
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, UK
I. W. Craig
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
B. Müller-Myhsok
Affiliation:
Max Planck Institute of Psychiatry, Munich, Germany
J. L. Kennedy
Affiliation:
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada Department of Psychiatry, University of Toronto, Canada
J. Strauss
Affiliation:
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada Department of Psychiatry, University of Toronto, Canada
J. B. Vincent
Affiliation:
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada Department of Psychiatry, University of Toronto, Canada
C. M. Lewis
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
A. E. Farmer
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
P. McGuffin
Affiliation:
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
*
*Address for correspondence: Mr R. A. Power, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London SE5 8AF, UK. (Email: robert.r.power@kcl.ac.uk)

Abstract

Background

Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.

Method

We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.

Results

A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).

Conclusions

These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012 

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