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

Humans vary substantially in their willingness to take risks. In a combined sample of over one 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. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Supplemental information may be found here:

Supplemental Information: http://humcap.uchicago.edu/RePEc/hka/wpaper/Linner ... ntal-information.pdf 
Supplemental Figures: http://humcap.uchicago.edu/RePEc/hka/wpaper/Linner ... analyses_figures.pdf 
Supplemental Tables: http://humcap.uchicago.edu/RePEc/hka/wpaper/Linner ... analyses_tables.xlsx 

Authors: 
Richard Karlsson Linnér, University Amsterdam
Pietro Biroli, University of Zurich
Edward Kong, Harvard University
Jonathan Beauchamp, University of Toronto
Daniel Benjamin, University of Southern California
Philipp Koellinger, University of Amsterdam
S. Fleur W. Meddens, University Amsterdam
Robee Wedow, University of Colorado, Boulder
Mark Alan Fontana, Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery
Maël Lebreton, University of Amsterdam
Abdel Abdellaoui, Vrije Universiteit Amsterdam
Anke R. Hammerschlag, University Amsterdam
Publication Date: 
November, 2018
Publication Status: 
Document Number: 
2018-087
File Description: 
First version, November 2018