A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank.
Shen X., Howard DM., Adams MJ., Hill WD., Clarke T-K., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium None., Deary IJ., Whalley HC., McIntosh AM.
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