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

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Nature communications. - 11, 1 (2020) , 2301, ISSN: 2041-1723

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2021
Urheber
Shen, Xueyi
Howard, David M.
Adams, Mark J.
Hill, W. David
Clarke, Toni-Kim
Deary, Ian J.
Whalley, Heather C.
McIntosh, Andrew M.
Domschke, Katharina

DOI
10.1038/s41467-020-16022-0
URN
urn:nbn:de:bsz:25-freidok-1757227
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15.08.2025, 07:29 MESZ

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  • 2021

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