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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

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

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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 (|r^g| ~ 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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Elements
Date Deposited: 28 Jan 2019 12:26
Last Modified: 28 Jan 2019 13:15
URI: http://repository.essex.ac.uk/id/eprint/23664

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