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

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


Title: A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Author: Shen, Xueyi
Sigurdsson, Engilbert   orcid.org/0000-0001-9404-7982
Stefansson, Kari   orcid.org/0000-0003-1676-864X
Date: 2020-05-08
Language: English
Scope: 2301
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Nature Communications;11(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-020-16022-0
Subject: Phenome-wide association; Mendelian Randomisation; Depression; Þunglyndi; Genarannsóknir
URI: https://hdl.handle.net/20.500.11815/2143

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Citation:

Shen, X., Howard, D.M., Adams, M.J. et al. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nature Communications 11, 2301 (2020). https://doi.org/10.1038/s41467-020-16022-0

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.

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Open Access This article is licensed under a Creative Commons Attribution 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 Creative Commons 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, visit http://creativecommons.org/licenses/by/4.0/.

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