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Genome-wide analysis of risk-taking behaviour and cross-disorder genetic correlations in 116,255 individuals from the UK Biobank cohort

By 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 Pell, Daniel J Smith, Valentina Escott-Price, Paul Harrison, Daniel J. Smith

Posted 16 Aug 2017
bioRxiv DOI: 10.1101/177014 (published DOI: 10.1038/s41398-017-0079-1)

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 to 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 which has a major impact on a range of common physical and mental health disorders.

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