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bioRxiv · 10.1101/177014

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

Strawbridge, R. J.·Ward, J.·Cullen, B.·Tunbridge, E. M.·Hartz, S.·Bierut, L.·Horton, A.·Bailey, M. E. S.·Graham, N.·Ferguson, A.·Lyall, D. M.·Mackay, D.·Pidgeon, L. M.·Cavanagh, J.·Pell, J. P.·O'Donovan, M.·Escott-Price, V.·Harrison, P. J.·Smith, D. J.
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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 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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Strawbridge, R. J., Ward, J., Cullen, B., Tunbridge, E. M., Hartz, S., Bierut, L., Horton, A., Bailey, M. E. S., Graham, N., Ferguson, A., Lyall, D. M., Mackay, D., Pidgeon, L. M., Cavanagh, J., Pell, J. P., O'Donovan, M., Escott-Price, V., Harrison, P. J., Smith, D. J.. 2017-08-16. Genome-wide analysis of risk-taking behaviour and cross-disorder genetic correlations in 116,255 individuals from the UK Biobank cohort. https://doi.org/10.1101/177014

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