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Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

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  • Aleix Arnau-Soler
  • Mark J Adams
  • Generation Scotland
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
  • Caroline Hayward
  • Pippa A Thomson

Abstract

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p

Suggested Citation

  • Aleix Arnau-Soler & Mark J Adams & Generation Scotland & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium & Caroline Hayward & Pippa A Thomson, 2018. "Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder," PLOS ONE, Public Library of Science, vol. 13(12), pages 1-29, December.
    • Handle: RePEc:plo:pone00:0209160
    DOI: 10.1371/journal.pone.0209160
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    1. Mengge Liu & Lu Wang & Yujie Zhang & Haoyang Dong & Caihong Wang & Yayuan Chen & Qian Qian & Nannan Zhang & Shaoying Wang & Guoshu Zhao & Zhihui Zhang & Minghuan Lei & Sijia Wang & Qiyu Zhao & Feng Li, 2024. "Investigating the shared genetic architecture between depression and subcortical volumes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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