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

, 23andMe Research Team, , , Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S. Fleur W. Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Stephen P. Tino, Abdel Abdellaoui, Anke R. Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A. Rietveld, Pascal N. Timshel, Maciej Trzaskowski, Ronald de VlamingChristian L. Zünd, Yanchun Bao, Laura Buzdugan, Ann H. Caplin, Chia Yen Chen, Peter Eibich, Pierre Fontanillas, Juan R. Gonzalez, Peter K. Joshi, Ville Karhunen, Aaron Kleinman, Remy Z. Levin, Christina M. Lill, Gerardus A. Meddens, Gerard Muntané, Sandra Sanchez-Roige, Frank J. van Rooij, Erdogan Taskesen, Yang Wu, Futao Zhang, Adam Auton, Jason D Boardman, David W Clark, Andrew Conlin, Jonathan P. Beauchamp

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
Early online date14 Jan 2019
DOIs
Publication statusPublished - 2019

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Keywords

  • Behavior/physiology
  • Case-Control Studies
  • Female
  • Genetic Loci/genetics
  • Genetic Predisposition to Disease/genetics
  • Genetics, Behavioral/methods
  • Genome-Wide Association Study/methods
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide/genetics

Cite this

, 23andMe Research Team, Karlsson Linnér, R., Biroli, P., Kong, E., Meddens, S. F. W., Wedow, R., Fontana, M. A., Lebreton, M., Tino, S. P., Abdellaoui, A., Hammerschlag, A. R., Nivard, M. G., Okbay, A., Rietveld, C. A., Timshel, P. N., Trzaskowski, M., ... Beauchamp, J. P. (2019). Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nature Genetics, 51(2), 245-257. https://doi.org/10.1038/s41588-018-0309-3