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

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Shen X., Howard D. M., Adams M. J., Hill W. D., Clarke T., McIntosh A. M., ...Daha Fazla

Nature Communications, cilt.11, sa.1, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1038/s41467-020-16022-0
  • Dergi Adı: Nature Communications
  • Derginin Tarandığı İndeksler: 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
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

© 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.