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

Coleman, J. R.I. et al. (2020) Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Molecular Psychiatry, 25(7), pp. 1430-1446. (doi: 10.1038/s41380-019-0546-6) (PMID:31969693) (PMCID:PMC7305950)

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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.

Item Type:Articles
Additional Information:This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). WJP was funded by NWO Veni grant 91619152. KLP acknowledges funding from the Alexander von Humboldt Foundation. KWC was funded in part by the National Institute of Mental Health (T32MH017119). NRW acknowledges funding from the Australian National Health and Medical Research Council (1078901 and 1087889). PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Lyall, Dr Donald
Authors: Coleman, J. R.I., Purves, K. L., Davis, K. A.S., Rayner, C., Choi, S. W., Hübel, C., Gaspar, H. A., Kan, C., Van der Auwera, S., Adams, M. J., Lyall, D. M., Peyrot, W. J., Dunn, E. C., Vassos, E., Danese, A., Grabe, H. J., Lewis, C. M., O’Reilly, P. F., McIntosh, A. M., Smith, D. J., Wray, N. R., Hotopf, M., Eley, T. C., and Breen, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Molecular Psychiatry
Publisher:Nature Research
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:23 January 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Molecular Psychiatry 25(7): 1430-1446
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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