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Genetics of self-re...
Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression
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- Strawbridge, RJ (author)
- Karolinska Institutet
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Ward, J (author)
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Lyall, LM (author)
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Tunbridge, EM (author)
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Cullen, B (author)
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Graham, N (author)
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Ferguson, A (author)
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Johnston, KJA (author)
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Lyall, DM (author)
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Mackay, D (author)
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Cavanagh, J (author)
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Howard, DM (author)
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Adams, MJ (author)
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Deary, I (author)
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Escott-Price, V (author)
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O'Donovan, M (author)
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McIntosh, AM (author)
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Bailey, MES (author)
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Pell, JP (author)
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Harrison, PJ (author)
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Smith, DJ (author)
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(creator_code:org_t)
- 2018-09-04
- 2018
- English.
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8:1, s. 178-
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Abstract
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- 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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Strawbridge, RJ
-
Ward, J
-
Lyall, LM
-
Tunbridge, EM
-
Cullen, B
-
Graham, N
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show more...
-
Ferguson, A
-
Johnston, KJA
-
Lyall, DM
-
Mackay, D
-
Cavanagh, J
-
Howard, DM
-
Adams, MJ
-
Deary, I
-
Escott-Price, V
-
O'Donovan, M
-
McIntosh, AM
-
Bailey, MES
-
Pell, JP
-
Harrison, PJ
-
Smith, DJ
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show less...
- Articles in the publication
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Translational ps ...
- By the university
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Karolinska Institutet