Department of Economics and Business Economics

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

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  • Xueyi Shen, University of Edinburgh
  • ,
  • David M Howard, University of Edinburgh, King’s College London
  • ,
  • Mark J Adams, University of Edinburgh
  • ,
  • W David Hill, University of Edinburgh
  • ,
  • Toni-Kim Clarke, University of Edinburgh
  • ,
  • Ian J Deary, University of Edinburgh
  • ,
  • Heather C Whalley, University of Edinburgh
  • ,
  • Andrew M McIntosh, University of Edinburgh
  • ,
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

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.

Original languageEnglish
JournalNature Communications
Pages (from-to)2301
Number of pages16
Publication statusPublished - 2020

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