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

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Shen, Xueyi
dc.contributor.author Sigurdsson, Engilbert
dc.contributor.author Stefansson, Kari
dc.date.accessioned 2020-10-27T15:45:44Z
dc.date.available 2020-10-27T15:45:44Z
dc.date.issued 2020-05-08
dc.identifier.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
dc.identifier.issn 2041-1723
dc.identifier.uri https://hdl.handle.net/20.500.11815/2143
dc.description Publisher's version (útgefin grein)
dc.description.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.
dc.description.sponsorship The present study is supported by a Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). Data acquisition and analyses were conducted using the UK Biobank Resource under approved project #4844. Participation of the UK Biobank subjects is gratefully appreciated. We also thank UK Biobank team for collecting and preparing data for analyses. Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. The PGC has received major funding from the US National Institute of Mental Health (5 U01MH109528-03). We thank the research participants and employees of 23andMe for supporting this study. X.S. receives support from China Scholarship Council (No. 201506040037). H.C.W. is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. D.M.H. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z) and a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Reference 27404). W.D.H. is supported by a grant from Age UK (Disconnected Mind Project). A.M.M. is supported by the Sackler Trust. I.J.D. is a participant in UK Biobank.
dc.format.extent 2301
dc.language.iso en
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartofseries Nature Communications;11(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Phenome-wide association
dc.subject Mendelian Randomisation
dc.subject Depression
dc.subject Þunglyndi
dc.subject Genarannsóknir
dc.title A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
dc.type info:eu-repo/semantics/article
dcterms.license 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/.
dc.description.version Peer Reviewed
dc.identifier.journal Nature Communications
dc.identifier.doi 10.1038/s41467-020-16022-0
dc.relation.url https://www.nature.com/articles/s41467-020-16022-0
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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