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

Coleman JRI 1 , Peyrot WJ 2 , Purves KL 1 , Davis KAS 3 , Rayner C 1 , Choi SW 1 Show all authors , Hübel C 1 , Gaspar HA 1 , Kan C 4 , Van der Auwera S 5 , Adams MJ 6 , Lyall DM 7 , Choi KW 8 , on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium , Dunn EC 9 , Vassos E 1 , Danese A 1 , Maughan B 1 , Grabe HJ 5 , Lewis CM 1 , O'Reilly PF 1 , McIntosh AM 6 , Smith DJ 7 , Wray NR 10 , Hotopf M 3 , Eley TC 11 , Breen G 12

Affiliations 

  • 1 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
  • 2 Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Medical Center, Amsterdam, the Netherlands
  • 3 NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
  • 4 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
  • 5 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
  • 6 Division of Psychiatry, University of Edinburgh, Edinburgh, UK
  • 7 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
  • 8 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
  • 9 Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • 10 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  • 11 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. [email protected]
  • 12 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. [email protected]
Mol Psychiatry, 2020 Jul;25(7):1430-1446.
PMID: 31969693 DOI: 10.1038/s41380-019-0546-6

Abstract

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 (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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