| Title: | A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank |
| Journal: | Nature Communications |
| Published: | 8 May 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32385265/ |
| DOI: | https://doi.org/10.1038/s41467-020-16022-0 |
| URL: | https://www.nature.com/articles/s41467-020-16022-0.pdf |
| Citations: | 99 (36 in last 2 years) as of 8 Aug 2024 |
Publication 3921
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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, 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.</p>
8 Authors
- Xueyi Shen
- David M. Howard
- Mark J. Adams
- W. David Hill
- Toni-Kim Clarke
- Ian J. Deary
- Heather C. Whalley
- Andrew M. McIntosh
Enabling scientific discoveries that improve human health