1. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences1
- Author
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Edward Kong, Pascal Timshel, Danielle Posthuma, Tõnu Esko, Maël Lebreton, Kathleen Mullan Harris, Philipp Koellinger, Murray B. Stein, Abraham A. Palmer, Urs Fischbacher, Robert J. Ursano, Erdogan Taskesen, Peter Eibich, Paul R. H. J. Timmers, Anke R. Hammerschlag, Ann H. Caplin, Jian Yang, Sandra Sanchez-Roige, Peter K. Joshi, Matthias Sutter, Pierre Fontanillas, Chia-Yen Chen, Albert Hofman, Patrick Turley, David A. Hinds, Futao Zhang, David Cesarini, Christina M. Lill, Laura Buzdugan, Ville Karhunen, Abdel Abdellaoui, S. Fleur W. Meddens, Henning Tiemeier, Christian L. Zund, Gert G. Wagner, Richard Karlsson Linnér, Lars Bertram, David W. Clark, Roy Thurik, André G. Uitterlinden, Maciej Trzaskowski, Mohammad Arfan Ikram, David Laibson, Cornelius A. Rietveld, Arcadi Navarro, Ernst Fehr, Yang Wu, Matthew B. McQueen, Ronald C. Kessler, Magnus Johannesson, Patrick J. F. Groenen, Gregor Hasler, James F. Wilson, Daniel Schunk, Stephen P. Tino, Pietro Biroli, Mark Alan Fontana, Juan R. González, Meena Kumari, Gerardus A. Meddens, Jonathan P. Beauchamp, Michelle N. Meyer, Jason D. Boardman, James J. Lee, Carlos Morcillo-Suarez, Aaron Kleinman, Minna Männikkö, Andrew Conlin, Adam Auton, Tune H. Pers, Michel G. Nivard, Ronald de Vlaming, Jon White, Robert Karlsson, Daniel J. Benjamin, Maarten Kooyman, Jacob Gratten, Aysu Okbay, Remy Z. Levin, Melissa C. Smart, Harriet de Wit, Conor C. Dolan, Frank J. A. van Rooij, Patrik K. E. Magnusson, Sonia Jain, Rauli Svento, Klaus M. Schmidt, Dorret I. Boomsma, Gerard Muntané, James MacKillop, Robbee Wedow, and Yanchun Bao
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Genetics ,0303 health sciences ,Gabaergic neurotransmission ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Phenotype ,03 medical and health sciences ,0302 clinical medicine ,SNP ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic association - Abstract
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 (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.
- Published
- 2018
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