TY  - JOUR
PY  - 2018//
TI  - Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression
JO  - Translational psychiatry
A1  - Strawbridge, Rona J.
A1  - Ward, Joey
A1  - Lyall, Laura M.
A1  - Tunbridge, Elizabeth M.
A1  - Cullen, Breda
A1  - Graham, Nicholas
A1  - Ferguson, Amy
A1  - Johnston, Keira J. A.
A1  - Lyall, Donald M.
A1  - Mackay, Daniel
A1  - Cavanagh, Jonathan
A1  - Howard, David M.
A1  - Adams, Mark J.
A1  - Deary, Ian
A1  - Escott-Price, Valentina
A1  - O'Donovan, Michael
A1  - McIntosh, Andrew M.
A1  - Bailey, Mark E. S.
A1  - Pell, Jill P.
A1  - Harrison, Paul J.
A1  - Smith, Daniel J.
SP  - 178
EP  - 178
VL  - 8
IS  - 1
N2  - 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 />  <p>Language: en</p>
LA  - en
SN  - 2158-3188
UR  - http://dx.doi.org/10.1038/s41398-018-0236-1
ID  - ref1
ER  -