Institut for Biomedicin

Preben Bo Mortensen

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

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DOI

  • Jonathan R. I. Coleman, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Wouter J. Peyrot, Vrije Univ Med Ctr, University of Amsterdam, Vrije Universiteit Amsterdam, VU UNIVERSITY MEDICAL CENTER, Dept Psychiat, Amsterdam UMC
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  • Kirstin L. Purves, Kings Coll London, Kings College London, University of London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr
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  • Katrina A. S. Davis, Kings Coll London, University of London, Kings College London, Dept Psychol Med, Inst Psychiat Psychol & Neurosci
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  • Christopher Rayner, Kings Coll London, Kings College London, University of London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr
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  • Shing Wan Choi, Kings Coll London, Kings College London, University of London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr
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  • Christopher Hubel, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Helena A. Gaspar, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Carol Kan, Kings Coll London, University of London, Kings College London, Dept Psychol Med, Inst Psychiat Psychol & Neurosci
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  • Sandra Van der Auwera, Univ Med Greifswald, Greifswald Medical School, Dept Psychiat & Psychotherapy
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  • Mark James Adams, Univ Edinburgh, Royal Infirmary of Edinburgh, University of Edinburgh, Royal Edinburgh Hosp, Div Psychiat
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  • Donald M. Lyall, Univ Glasgow, University of Glasgow, Inst Hlth & Wellbeing
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  • Karmel W. Choi, Massachusetts Gen Hosp, Harvard University, Massachusetts General Hospital, Psychiat & Neurodev Genet Unit, Ctr Genom Med
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  • Psychiat Genomics Consortium
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  • Erin C. Dunn, Harvard Med Sch, Harvard University, Harvard Medical School, Dept Psychiat
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  • Evangelos Vassos, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Andrea Danese, South London & Maudsley NHS Fdn Trust, South London & Maudsley NHS Trust, Natl & Specialist CAMHS Trauma & Anxiety Clin
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  • Barbara Maughan, Kings Coll London, Kings College London, University of London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr
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  • Hans J. Grabe, Univ Med Greifswald, Greifswald Medical School, Dept Psychiat & Psychotherapy
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  • Cathryn M. Lewis, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Paul F. O'Reilly, Kings Coll London, Kings College London, University of London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr
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  • Andrew M. McIntosh, Univ Edinburgh, Royal Infirmary of Edinburgh, University of Edinburgh, Royal Edinburgh Hosp, Div Psychiat
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  • Daniel J. Smith
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  • Naomi R. Wray, Univ Queensland, University of Queensland, Queensland Brain Inst
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  • Matthew Hotopf, Kings Coll London, University of London, Kings College London, Dept Psychol Med, Inst Psychiat Psychol & Neurosci
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  • Thalia C. Eley, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr
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  • Gerome Breen, South London & Maudsley NHS Trust, South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (r(g) = 0.24, p = 1.8 x 10(-7) versus r(g) = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 x 10(-4)). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

OriginalsprogEngelsk
TidsskriftMolecular Psychiatry
Vol/bind25
Nummer7
Sider (fra-til)1430-1446
Antal sider17
ISSN1359-4184
DOI
StatusUdgivet - 2020

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