Háskóli ÍslandsUniversity of IcelandShen, XueyiSigurdsson, EngilbertStefansson, Kari2020-10-272020-10-272020-05-08Shen, 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/s41467-020-16022-02041-1723https://hdl.handle.net/20.500.11815/2143Publisher's version (útgefin grein)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.2301eninfo:eu-repo/semantics/openAccessPhenome-wide associationMendelian RandomisationDepressionÞunglyndiGenarannsóknirinfo:eu-repo/semantics/articleNature Communications10.1038/s41467-020-16022-0