LAUSR

Background Risk-taking is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use and diet. Risk-taking behaviour therefore fits within the Research Domain Criteria (RDoC) approach, whereby elucidation of the genetic determinants of this trait has the potential to improve our understanding of behaviours that span a number of psychiatric disorders. Methods A genome wide association study was conducted in 116 255 UK Biobank participants who responded yes/no to the question “would you consider yourself a risk-taker?”. Genetic correlations were calculated between risk-taking and phenotypes relevant to psychiatric disorders. Expression quantitative trait loci analyses in the brain were conducted for significant loci. Results Risk-takers (compared to controls) were more likely to be men, smokers and have a history of mental illness. Significant loci associated with risk-taking behaviour were identified on chromosomes 3 (rs13084531) and 6 (rs9379971). The effect of rs13084531 was comparable between men and women, whilst rs9379971 showed stronger effects in women than men. Rs13084531 on chromosome 3 demonstrated significant effects on CADM2 mRNA expression levels. CADM2 has previously been implicated in cognition, including executive function. The chromosome 6 locus remains challenging to interpret due to the complexity of the HLA region, although a number of testis-specific genes were observed in this locus. Genetic susceptibility for risk-taking behaviour was significantly correlated with schizophrenia (rg 0.27 p= 4.54⁎10–11), bipolar disorder (rg 0.26 p= 1.73⁎10-4), attention-deficit hyperactivity disorder (rg 0.31 p= 0.0132) and post-traumatic stress disorder (rg 0.51 p= 0.0018), as well as with smoking (rg 0.17 p= 0.0102)and total obesity (rg 0.10 p= 0.0028). Discussion Despite being based on only a single question, this study identified genetic determinants of risk-taking behaviour and further demonstrated genetic correlation with psychiatric disorders where this trait is a feature. Although it is not clear which subtypes of risk-taking behaviour are being assessed, these findings further our understanding of the biology of risk-taking behaviour, a trait which has a major impact on a broad spectrum of physical and mental disorders.