Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression
Harrison, Paul J
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Strawbridge, R; Ward, Joey; Lyall, Laura; Tunbridge, Elizabeth; Cullen, Breda; Graham, Nicholas; Ferguson, AGenetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expressionmy; Johnston, Keira; Lyall, Donald; MacKay,Daniel; Cavanagh, Jonathan; Howard, David; Adams, Mark; Deary, Ian; Escott-Price, Valentina; O'Donovan, Michael; McIntosh, Andrew; Bailey, Mark; Bell, Jill; Harrison, Paul; Smith, Daniel. Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression. Translational Pyschiatry (8) 2018, 178 el;
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.
https://doi.org/10.1038/s41398-018-0236-1 This is an Open Access article under the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). Eligible users can access the full text via NHS OpenAthens at [https://www.nature.com/articles/s41398-018-0236-1].