Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

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  • dc.contributor.author Karlsson Linnér, Richard
  • dc.contributor.author González, Juan Ramón
  • dc.contributor.author Muntané, Gerard
  • dc.contributor.author Morcillo Suárez, Carlos, 1969-
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
  • dc.contributor.author Beauchamp, Jonathan P.
  • dc.date.accessioned 2023-04-26T17:08:44Z
  • dc.date.available 2023-04-26T17:08:44Z
  • dc.date.issued 2019
  • dc.description.abstract Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.
  • dc.description.sponsorship This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Karlsson Linnér R, Biroli P, Kong E, Meddens SFW, Wedow R, Fontana MA et al. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nat Genet. 2019;51(2):245-57. DOI: 10.1038/s41588-018-0309-3
  • dc.identifier.doi http://dx.doi.org/10.1038/s41588-018-0309-3
  • dc.identifier.issn 1061-4036
  • dc.identifier.uri http://hdl.handle.net/10230/56575
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Genet. 2019;51(2):245-57
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/647648
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/647648
  • dc.rights © Springer Nature Publishing AG. Karlsson Linnér R, Biroli P, Kong E, Meddens SFW, Wedow R, Fontana MA et al. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nat Genet. 2019;51(2):245-57. DOI 10.1038/s41588-018-0309-3 [http://dx.doi.org/10.1038/s41588-018-0309-3]
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.keyword Behavioural genetics
  • dc.subject.keyword Genome-wide association studies
  • dc.title Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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