| Title: | Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression |
| Journal: | Translational Psychiatry |
| Published: | 4 Sep 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30181555/ |
| DOI: | https://doi.org/10.1038/s41398-018-0236-1 |
| URL: | https://www.nature.com/articles/s41398-018-0236-1.pdf |
| Citations: | 32 (6 in last 2 years) as of 8 Aug 2024 |
Publication 4987
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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.</p>
21 Authors
- 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. Harrison
- Daniel J. Smith
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