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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 ,
T. Wingenbach ,
S. Cohen-Woods ,
R. Uher ,
M. Y. Ng ,
A. W. Butler ,
M. Ising ,
N. Craddock ,
M. J. Owen  and
A. Korszun
...Show all authors
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: [email protected])
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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.

Keywords

GCTAheritability of environmentpersonalitystressful life events
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 9 , September 2013 , pp. 1965 - 1971
Copyright
Copyright © Cambridge University Press 2012 

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References

Andrews, G (1981). A prospective study of life events and psychological symptoms. Psychological Medicine 11, 795–801.CrossRefGoogle ScholarPubMed
Bebbington, P, Wilkins, S, Jones, P, Foerster, A, Murray, R, Toone, B, Lewis, S (1993). Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study. British Journal of Psychiatry 162, 72–79.CrossRefGoogle ScholarPubMed
Bemmels, HR, Burt, SA, Legrand, LN, Iacono, WG, McGue, M (2008). The heritability of life events: an adolescent twin and adoption study. Twin Research and Human Genetics 11, 257–265.CrossRefGoogle ScholarPubMed
Billig, JP, Hershberger, SL, Iacono, WG, McGue, M (1996). Life events and personality in late adolescence: genetic and environmental relations. Behavior Genetics 26, 543–554.CrossRefGoogle ScholarPubMed
Boardman, JD, Alexander, KB, Stallings, MC (2011). Stressful life events and depression among adolescent twin pairs. Biodemography and Social Biology 57, 53–66.CrossRefGoogle ScholarPubMed
Brugha, T, Bebbington, P, Tennant, C, Hurry, J (1985). The List of Threatening Experiences: a subset of 12 life event categories with considerable long-term contextual threat. Psychological Medicine 15, 189–194.CrossRefGoogle ScholarPubMed
Cohen-Woods, S, Gaysina, D, Craddock, N, Farmer, A, Gray, J, Gunasinghe, C, Hoda, F, Jones, L, Knight, J, Korszun, A, Owen, MJ, Sterne, A, Craig, IW, McGuffin, P (2009). Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder. Human Molecular Genetics 18, 1504–1509.CrossRefGoogle ScholarPubMed
Dudbridge, F, Gusnanto, A (2008). Estimation of significance thresholds for genomewide association scans. Genetic Epidemiology 32, 227–234.CrossRefGoogle ScholarPubMed
Eysenck, HJ, Eysenck, SBG (1975). Manual of the Eysenck Personality Questionnaire. Hodder and Stoughton: Sevenoaks, Kent.Google Scholar
Eysenck, SBG, Eysenck, HJ, Barrett, P (1985). A revised version of the psychoticism scale. Personality and Individual Differences 6, 21–29.CrossRefGoogle Scholar
Farmer, A, Breen, G, Brewster, S, Craddock, N, Gill, M, Korszun, A, Maier, W, Middleton, L, Mors, O, Owen, M, Perry, J, Preisig, M, Rietschel, M, Reich, T, Jones, L, Jones, I, McGuffin, P (2004). The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study. BMC Psychiatry 4, 42.CrossRefGoogle Scholar
Farmer, A, Redman, K, Harris, T, Mahmood, A, Sadler, S, Pickering, A, McGuffin, P (2002). Neuroticism, extraversion, life events and depression. The Cardiff Depression Study. British Journal of Psychiatry 181, 118–122.Google ScholarPubMed
Gaysina, D, Cohen-Woods, S, Chow, PC, Martucci, L, Schosser, A, Ball, HA, Tozzi, F, Perry, J, Muglia, P, Craig, IW, McGuffin, P, Farmer, A (2009). Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case-control study (BACCS). American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 150B, 836–844.CrossRefGoogle Scholar
Kandler, C, Bleidorn, W, Riemann, R, Angleitner, A, Spinath, FM (2012). Life events as environmental states and genetic traits and the role of personality: a longitudinal twin study. Behavior Genetics 42, 57–72.CrossRefGoogle ScholarPubMed
Kendler, KS, Baker, JH (2007). Genetic influences on measures of the environment: a systematic review. Psychological Medicine 37, 615–626.CrossRefGoogle ScholarPubMed
Kendler, KS, Karkowski, LM, Prescott, CA (1999 a). The assessment of dependence in the study of stressful life events: validation using a twin design. Psychological Medicine 29, 1455–1460.CrossRefGoogle Scholar
Kendler, KS, Karkowski, LM, Prescott, CA (1999 b). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry 156, 837–841.CrossRefGoogle ScholarPubMed
Kendler, KS, Neale, M, Kessler, R, Heath, A, Eaves, L (1993). A twin study of recent life events and difficulties. Archives of General Psychiatry 50, 789–796.CrossRefGoogle ScholarPubMed
Kennedy, S, Thompson, R, Stancer, HC, Roy, A, Persad, E (1983). Life events precipitating mania. British Journal of Psychiatry 142, 398–403.CrossRefGoogle ScholarPubMed
Kessing, LV, Agerbo, E, Mortensen, PB (2004). Major stressful life events and other risk factors for first admission with mania. Bipolar Disorders 6, 122–129.CrossRefGoogle ScholarPubMed
Lewis, CM, Ng, MY, Butler, AW, Cohen-Woods, S, Uher, R, Pirlo, K, Weale, ME, Schosser, A, Paredes, UM, Rivera, M, Craddock, N, Owen, MJ, Jones, L, Jones, I, Korszun, A, Aitchison, KJ, Shi, JX, Quinn, JP, MacKenzie, A, Vollenweider, P, Waeber, G, Heath, S, Lathrop, M, Muglia, P, Barnes, MR, Whittaker, JC, Tozzi, F, Holsboer, F, Preisig, M, Farmer, AE, Breen, G, Craig, IW, McGuffin, P (2010). Genome-wide association study of major recurrent depression in the UK population. American Journal of Psychiatry 167, 949–957.CrossRefGoogle Scholar
Muglia, P, Tozzi, F, Galwey, NW, Francks, C, Upmanyu, R, Kong, XQ, Antoniades, A, Domenici, E, Perry, J, Rothen, S, Vandeleur, CL, Mooser, V, Waeber, G, Vollenweider, P, Preisig, M, Lucae, S, Muller-Myhsok, B, Holsboer, F, Middleton, LT, Roses, AD (2010). Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts. Molecular Psychiatry 15, 589–601.CrossRefGoogle ScholarPubMed
Pickering, A, Farmer, A, Harris, T, Redman, K, Mahmood, A, Sadler, S, McGuffin, P (2003). A sib-pair study of psychoticism, life events and depression. Personality and Individual Differences 34, 613–623.CrossRefGoogle Scholar
Plomin, R, Lichtenstein, P, Pedersen, NL, McClearn, GE, Nesselroade, JR (1990). Genetic influence on life events during the last half of the life span. Psychology and Aging 5, 25–30.CrossRefGoogle ScholarPubMed
Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MAR, Bender, D, Maller, J, Sklar, P, de Bakker, PIW, Daly, MJ, Sham, PC (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics 81, 559–575.CrossRefGoogle ScholarPubMed
Saudino, KJ, Pedersen, NL, Lichtenstein, P, McClearn, GE, Plomin, R (1997). Can personality explain genetic influences on life events? Journal of Personality and Social Psychology 72, 196–206.CrossRefGoogle ScholarPubMed
StataCorp (2011). Stata Statistical Software: Release 12. StataCorp LP: College Station, TX.Google Scholar
Thapar, A, McGuffin, P (1996). Genetic influences on life events in childhood. Psychological Medicine 26, 813–820.CrossRefGoogle ScholarPubMed
Tozzi, F, Prokopenko, I, Perry, JD, Kennedy, JL, McCarthy, AD, Holsboer, F, Berrettini, W, Middleton, LT, Chilcoat, HD, Muglia, P (2008). Family history of depression is associated with younger age of onset in patients with recurrent depression. Psychological Medicine 38, 641–649.CrossRefGoogle ScholarPubMed
Woods, NF, Dery, GK, Most, A (1982). Stressful life events and perimenstrual symptoms. Journal of Human Stress 8, 23–31.CrossRefGoogle ScholarPubMed
Yang, JA, Lee, SH, Goddard, ME, Visscher, PM (2011). GCTA: a tool for genome-wide complex trait analysis. American Journal of Human Genetics 88, 76–82.CrossRefGoogle ScholarPubMed