Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression

Rona J Strawbridge, Joey Ward, Laura M Lyall, Elizabeth M Tunbridge, Breda Cullen, Nicholas Graham, Amy Ferguson, Keira J A Johnston, Donald M Lyall, Daniel Mackay, Jonathan Cavanagh, David M Howard, Mark J Adams, Ian Deary, Valentina Escott-Price, Michael O'Donovan, Andrew M McIntosh, Mark E S Bailey, Jill P Pell, Paul J HarrisonDaniel J Smith

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-11
JournalTranslational Psychiatry
Volume8
Issue number1
Early online date4 Sep 2018
DOIs
Publication statusE-pub ahead of print - 4 Sep 2018

Keywords

  • ADHD
  • genetics
  • pathogenesis
  • schizophrenia

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