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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

By Robert Karlsson, Pietro Biroli, Edward Kong, S Fleur W Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Abdel Abdellaoui, Anke R Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A. Rietveld, Pascal N Timshel, Stephen P Tino, Maciej Trzaskowski, Ronald de Vlaming, Christian 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, 23andMe Research Team, eQTLgen Consortium, International Cannabis Consortium, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium,, Adam Auton, Jason D. Boardman, David W Clark, Andrew Conlin, Conor C Dolan, Urs Fischbacher, Patrick JF Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A Ikram, Sonia Jain, Ronald C Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suarez, Matthew B. McQueen, Klaus M Schmidt, Melissa C Smart, Matthias Sutter, A Roy Thurik, Andre G Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret Boomsma, Tõnu Esko, Ernst Fehr, David A. Hinds, Magnus Johannesson, Meena Kumari, David Laibson, Patrik K.E. Magnusson, Michelle N Meyer, Arcadi Navarro, Abraham A. Palmer, Tune H. Pers, Danielle Posthuma, Daniel Schunk, Murray B. Stein, Rauli Svento, Henning Tiemeier, Paul RHJ Timmers, Patrick Turley, Robert J Ursano, Gert G Wagner, James F Wilson, Jacob Gratten, James J Lee, David Cesarini, Daniel J Benjamin, Philipp D Koellinger, Tonu Esko

Posted 08 Feb 2018
bioRxiv DOI: 10.1101/261081

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 (|rˆg| ~ 0.25 to 0.50) 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.

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