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

Publication type

Journal Article

Published in

Nature Genetics

Authors

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 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, Adam Auton, Jason D. Boardman, David W. Clark, Andrew Conlin, Conor C. Dolan, Urs Fischbacher, Patrick J. F. Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A. Ikram, Sonia Jain, Robert Karlsson, Ronald C. Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suarez, Matthew B. McQueen, Klaus M. Schmidt, Melissa Smart, Matthias Sutter, A. Roy Thurik, André G. Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret I. 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 R. H. J. 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 and Jonathan P. Beauchamp

Publication date

Summary

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 ( rg ~ 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.

DOI

https://doi.org/10.1038/s41588-018-0309-3

ISSN

16

Subjects

Drug/Alcohol Abuse, Social Behaviour, Biology and Genetics

Notes

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