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.

Details

Title
Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression
Author
Strawbridge, Rona J 1   VIAFID ORCID Logo  ; Ward, Joey 2 ; Lyall, Laura M 2 ; Tunbridge, Elizabeth M 3 ; Cullen, Breda 2   VIAFID ORCID Logo  ; Graham, Nicholas 2 ; Ferguson, Amy 2 ; Johnston, Keira J A 4 ; Lyall, Donald M 2 ; Mackay, Daniel 2 ; Cavanagh, Jonathan 2 ; Howard, David M 5   VIAFID ORCID Logo  ; Adams, Mark J 5   VIAFID ORCID Logo  ; Deary, Ian 6 ; Escott-Price, Valentina 7   VIAFID ORCID Logo  ; Michael O’Donovan 7   VIAFID ORCID Logo  ; McIntosh, Andrew M 5   VIAFID ORCID Logo  ; Bailey, Mark E S 8   VIAFID ORCID Logo  ; Pell, Jill P 2 ; Harrison, Paul J 3   VIAFID ORCID Logo  ; Smith, Daniel J 2   VIAFID ORCID Logo 

 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden 
 Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK 
 Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK 
 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 
 Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK 
 Department of Psychology, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 
 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK 
 School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK 
Pages
1-11
Publication year
2018
Publication date
Sep 2018
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2099432944
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.