A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 32385265.
- Also identified by DOI 10.1038/s41467-020-16022-0 and PMC identifier 7210889.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>FDR</sub> < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p<sub>FDR</sub>: 0.049 to 1.28 × 10<sup>-14</sup>) 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.
Medical subject headings
- Depression
- Prefrontal Cortex