Genome-Wide Association Analyses of Risk Tolerance and Risky Behaviors in over 1 Million Individuals Identify Hundreds of Loci and Shared Genetic Influences

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Citation

Karlsson Linner, Richard; Biroli, Pietro; Kong, Edward; Meddens, S. Fleur W.; Wedow, Robbee; Fontana, Mark Alan; Lebreton, Mael; Tino, Stephen P.; Abdellaoui, Abdel; & Hammerschlag, Anke R., et al. (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, 245-257. PMCID: PMC6713272

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 ([Formula: see text] ~ 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.

URL

http://dx.doi.org/10.1038/s41588-018-0309-3

Reference Type

Journal Article

Year Published

2019

Journal Title

Nature Genetics

Author(s)

Karlsson Linner, Richard
Biroli, Pietro
Kong, Edward
Meddens, S. Fleur W.
Wedow, Robbee
Fontana, Mark Alan
Lebreton, Mael
Tino, Stephen P.
Abdellaoui, Abdel
Hammerschlag, Anke R.
Nivard, Michel G.
Okbay, Aysu
Rietveld, Cornelius A.
Timshel, Pascal N.
Trzaskowski, Maciej
Vlaming, Ronald de
Zund, Christian L.
Bao, Yanchun
Buzdugan, Laura
Caplin, Ann H.
Chen, Chia-Yen
Eibich, Peter
Fontanillas, Pierre
Gonzalez, Juan Ramon
Joshi, Peter K.
Karhunen, Ville
Kleinman, Aaron
Levin, Remy Z.
Lill, Christina M.
Meddens, Gerardus A.
Muntane, Gerard
Sanchez-Roige, Sandra
van Rooij, Frank J. A.
Taskesen, Erdogan
Wu, Yang
Zhang, Futao
23andMe Research Team,
eQTLgen Consortium,
International Cannabis Consortium,
Social Science Genetic Association Consortium,
Auton, Adam
Boardman, Jason D.
Clark, David W.
Conlin, Andrew
Dolan, Conor C.
Fischbacher, Urs
Groenen, Patrick J. F.
Harris, Kathleen Mullan
Hasler, Gregor
Hofman, Albert
Ikram, Mohammad A.
Jain, Sonia
Karlsson, Robert
Kessler, Ronald C.
Kooyman, Maarten
MacKillop, James
Mannikko, Minna
Morcillo-Suarez, Carlos
McQueen, Matthew B.
Schmidt, Klaus M.
Smart, Melissa C.
Sutter, Matthias
Thurik, A. Roy
Uitterlinden, Andre G.
White, Jon
de Wit, Harriet
Yang, Jian
Bertram, Lars
Boomsma, Dorret I.
Esko, Tonu
Fehr, Ernst
Hinds, David A.
Johannesson, Magnus
Kumari, Meena
Laibson, David I.
Magnusson, Patrik K. E.
Meyer, Michelle N.
Navarro, Arcadi
Palmer, Abraham A.
Pers, Tune H.
Posthuma, Danielle
Schunk, Daniel
Stein, Murray B.
Svento, Rauli
Tiemeier, Henning
Timmers, Paul R. H. J.
Turley, Patrick
Ursano, Robert J.
Wagner, Gert G.
Wilson, James F.
Gratten, Jacob
Lee, James J.
Cesarini, David
Benjamin, Daniel J.
Koellinger, Philipp D.
Beauchamp, Jonathan P.

PMCID

PMC6713272

ORCiD

Harris, KM - 0000-0001-9757-1026