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

Strawbridge, R. et al. (2018) Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression. Translational Psychiatry, 8, 178. (doi: 10.1038/s41398-018-0236-1) (PMID:30181555) (PMCID:PMC6123450)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel and Cullen, Dr Breda and O'Donovan, Professor Michael and Mackay, Professor Daniel and Graham, Dr Nicholas and Lyall, Dr Laura and Bailey, Dr Mark and Cavanagh, Professor Jonathan and Ward, Dr Joey and Johnston, Ms Keira and Pell, Professor Jill and Ferguson, Amy and Lyall, Dr Donald and Strawbridge, Dr Rona
• Authors: Strawbridge, R., Ward, J., Lyall, L. M., Turnbridge, E. M., Cullen, B., Graham, N., Ferguson, A., Johnston, K. J.A., Lyall, D. M., Mackay, D., Cavanagh, J., Howard, D. M., Adams, M. J., Deary, I., Escott-Price, V., O'Donovan, M., McIntosh, A. M., Bailey, M. E.S., Pell, J. P., Harrison, P. J., and Smith, D.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Translational Psychiatry
• Publisher: Nature Publishing Group
• ISSN: 2158-3188
• ISSN (Online): 2158-3188
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Translational Psychiatry 8:178
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131	0	Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health