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

A Correction to this article was published on 18 May 2020

This article has been updated

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.

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Code availability

Analytical code underlying this project will be made available at https://github.com/tnggroup.

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Acknowledgements

We thank the members of the UK Biobank Mental Health Genetics Group for their valuable discussion and feedback on this work. We are also deeply indebted to the scientists involved in the construction of the UK Biobank, and to the investigators who comprise the PGC. Finally, we thank the hundreds of thousands of subjects who have shared their life experiences with investigators in the UK Biobank and the PGC. This research has been conducted using the UK Biobank Resource, as an approved extension to application 16577 (Dr Breen). 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. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. 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).

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

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Coleman, J.R.I., Peyrot, W.J., Purves, K.L. et al. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Mol Psychiatry 25, 1430–1446 (2020). https://doi.org/10.1038/s41380-019-0546-6

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