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

Coleman, Jonathan R.I., Peyrot, Wouter J., Purves, Kirstin L., Davis, Katrina A.S., Rayner, Christopher, Choi, Shing Wan, Hübel, Christopher, Gaspar, Héléna A., Kan, Carol, Van der Auwera, Sandra, Adams, Mark James, Lyall, Donald M., Choi, Karmel W., PGC MDD Working Group, , Dunn, Erin C., Vassos, Evangelos, Danese, Andrea, Maughan, Barbara, Grabe, Hans J., Lewis, Cathryn M., O'Reilly, Paul F., McIntosh, Andrew M., Smith, Daniel J., Wray, Naomi R., Hotopf, Matthew, Eley, Thalia C., and Breen, Gerome (2020) Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Molecular Psychiatry, 25. pp. 1430-1446.

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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.

Item ID: 62264
Item Type: Article (Research - C1)
ISSN: 1476-5578
Copyright Information: © The Author(s), under exclusive licence to Springer Nature Limited 2020
Funders: National Institute for Health Research Biomedical Research Centre (NIHRBRC), King's College, London (KCL), Guy's & St Thomas' Foundation (GSTT), Maudsley Charity (MC), Netherlands Organisation for Scientific Research (NWO), Alexander von Humboldt Foundation (AVHF), National Institute of Mental Health (NIMH), Australian National Health and Medical Research Council (NHMRC), US National Institute of Drug Abuse (NIDA)
Projects and Grants: GSTT TR130505, MC 980, NWO Veni grant 91619152, NIMH T32MH017119, NHMRC 1078901, NHMRC 1087889, NIDA U01 MH109528, NIDA U01 MH1095320
Date Deposited: 12 Feb 2020 07:32
FoR Codes: 52 PSYCHOLOGY > 5202 Biological psychology > 520201 Behavioural genetics @ 100%
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