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Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort

  • Rona J. Strawbridge
  • , Joey Ward
  • , Breda Cullen
  • , Elizabeth M. Tunbridge
  • , Sarah Hartz
  • , Laura Bierut
  • , Amy Horton
  • , Mark E.S. Bailey
  • , Nicholas Graham
  • , Amy Ferguson
  • , Donald M. Lyall
  • , Daniel Mackay
  • , Laura M. Pidgeon
  • , Jonathan Cavanagh
  • , Jill P. Pell
  • , Michael O'Donovan
  • , Valentina Escott-Price
  • , Paul J. Harrison
  • , Daniel J. Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use, and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome-wide association study in 116,255 UK Biobank participants who responded yes/no to the question "Would you consider yourself a risk taker?" Risk takers (compared with controls) were more likely to be men, smokers, and have a history of psychiatric disorder. Genetic loci associated with risk-taking behaviour were identified on chromosomes 3 (rs13084531) and 6 (rs9379971). The effects of both lead SNPs were comparable between men and women. The chromosome 3 locus highlights CADM2, previously implicated in cognitive and executive functions, but the chromosome 6 locus is challenging to interpret due to the complexity of the HLA region. Risk-taking behaviour shared significant genetic risk with schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and post-traumatic stress disorder, as well as with smoking and total obesity. Despite being based on only a single question, this study furthers our understanding of the biology of risk-taking behaviour, a trait that has a major impact on a range of common physical and mental health disorders.

Original languageEnglish
Article number39
JournalTranslational psychiatry
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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