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Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder

Mullins, N. and Power, R.A. and Fisher, H.L. and Hanscombe, K.B. and Euesden, J. and Iniesta, R. and Levinson, D.F. and Weissman, M.M. and Potash, J.B. and Shi, J. and Uher, R. and Cohen-Woods, S. and Rivera, M. and Jones, Lisa and Jones, I. and Craddock, N. and Owen, M.J. and Korszun, A. and Craig, I.W. and Farmer, A.E. and McGuffin, P. and Breen, G. and Lewis, C.M. (2016) Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder. Psychological Medicine, 46 (4). pp. 759-770. ISSN Print:0033-2917 Online: 1469-8978

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Abstract

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

Item Type: Article
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Uncontrolled Keywords: depression, genetics, gene-environment interactions, polygenic risk scoring
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Copyright Info: Open access article
Depositing User: Lisa Jones
Date Deposited: 04 Oct 2016 07:18
Last Modified: 04 Oct 2016 07:18
URI: https://eprints.worc.ac.uk/id/eprint/4954

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