A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Nature Communications, vol.11, no.1, 2020 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 11 Issue: 1
- Publication Date: 2020
- Doi Number: 10.1038/s41467-020-16022-0
- Journal Name: Nature Communications
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Geobase, INSPEC, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
- Open Archive Collection: AVESIS Open Access Collection
- Dokuz Eylül University Affiliated: No
Abstract
© 2020, The Author(s).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.