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

  • 23and Me Research Team
  • , eQTLgen Consortium
  • , International Cannabis Consortium
  • , Social Science Genetic Association Consortium
  • Department of Complex Trait Genetics
  • Vrije Universiteit Amsterdam
  • Erasmus University Rotterdam
  • Department of Economics
  • Department of Economics
  • University of Zurich
  • Harvard University
  • Broad Institute
  • Department of Epidemiology
  • Analytic and Translational Genetics Unit
  • Massachusetts General Hospital
  • Center for the Advancement of Value in Musculoskeletal Care
  • Hospital for Special Surgery - New York
  • Department of Healthcare Policy and Research
  • Cornell University
  • Amsterdam School of Economics
  • University of Amsterdam
  • Amsterdam Brain and Cognition
  • Department of Economics
  • University of Toronto
  • Department of Biological Psychology
  • Department of Applied Economics
  • Department of Epidemiology
  • University of Copenhagen
  • Department of Epidemiology Research
  • Statens Serum Institut
  • Institute for Molecular Bioscience
  • University of Queensland
  • University of Essex
  • Seminar for Statistics
  • ETH Zurich—Institute for Particle Physics and Astrophysics (IPA)
  • Stuyvesant High School
  • Psychiatric and Neurodevelopmental Genetics Unit
  • University of Oxford
  • Socio-Economic Panel Study
  • German Institute for Economic Research
  • Max Planck Institute for Demographic Research
  • Research
  • 23andMe Inc.
  • Barcelona Institute for Global Health
  • Pompeu Fabra University
  • Biomedical Research Networking Center in Epidemiology and Public Health (CiberESP)
  • Centre for Global Health Research
  • University of Edinburgh
  • Centre for Life Course Health Research
  • University of Oulu
  • University of California at San Diego
  • Genetic and Molecular Epidemiology Group
  • University of Lübeck
  • Team Loyalty BV
  • Departament de Ciències Experimentals i de la Salut
  • Research Department
  • Institut d’Investigació Sanitària Pere Virgili (IISPV)
  • San Juan de Dios Sanitary Park

Research output: Contribution to journal › Article › peer-review

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 (∣r̂ g∣ ~ 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.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalNature Genetics
Volume51
Issue number2
DOIs
Publication statusPublished - 14 Jan 2019
Externally publishedYes

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