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A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank.
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Nature communications
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2020-05-08
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11
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1
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2301
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s41467-020-16022-0.pdf
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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, p < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p: 0.049 to 1.28 × 10) 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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Shen X, Howard DM, Adams MJ, Hill WD, Clarke TK; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Deary IJ, Whalley HC, McIntosh AM. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nat Commun. 2020 May 8;11(1):2301. doi: 10.1038/s41467-020-16022-0. PMID: 32385265; PMCID: PMC7210889.