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
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature communications. - 11, 1 (2020) , 2301, ISSN: 2041-1723
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2021
- Urheber
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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
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10.1038/s41467-020-16022-0
- URN
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urn:nbn:de:bsz:25-freidok-1757227
- Rechteinformation
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- Letzte Aktualisierung
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15.08.2025, 07:29 MESZ
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Beteiligte
- 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
- Universität
Entstanden
- 2021