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Abstract
Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.
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1 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
2 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
3 Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK
4 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK; Division of Psychiatry, College of Medicine, University of Edinburgh, Edinburgh, UK
5 Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
6 Department of Psychology, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
7 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
8 School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK