A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Shen, Xueyi, Howard, David M., Adams, Mark J., Hill, W. David, Clarke, Toni Kim, Psychiatric Genomics Consortium, , Deary, Ian J., Whalley, Heather C., and Mcintosh, Andrew M. (2020) A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nature Communications, 11 (1). 2301.

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Abstract

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10−14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

Item ID: 67951
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: Open Access. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Additional Information:

Grant Sinnamon is a member of the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Funders: Wellcome Trust (WT), Medical Research Council (MRC)
Projects and Grants: WT 104036/Z/14/Z, MRC MC_PC_17209
Date Deposited: 03 May 2021 23:32
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320221 Psychiatry (incl. psychotherapy) @ 100%
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