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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 influences1

Authors
Qiang Lin,Pietro Biroli
Edward Kong,S Meddens,Robbee Wedow,Mark Fontana,Maël Lebreton,Abdel Abdellaoui,Anke Hammerschlag,Michel Nivard,Aysu Okbay,Cornelius Rietveld,Pascal Timshel,Stephen Tino,Maciej Trzaskowski,Ronald Vlaming,Christian Zünd,Yanchun Bao,Laura Buzdugan,Ann Caplin,Chia-Yen Chen,Peter Eibich,Pierre Fontanillas,Juan Gonzalez,Peter Joshi,Ville Karhunen,Aaron Kleinman,Remy Levin,Christina Lill,Gerardus Meddens,Gerard Muntané,Sandra Sanchez-Roige,Frank Rooij,Erdogan Taskesen,Yang Wu,Futao Zhang,23andMe Consortium,,Adam Auton,Jason Boardman,David Clark,Andrew Conlin,Conor Dolan,Urs Fischbacher,Patrick Groenen,Kathleen Harris,Gregor Hasler,Albert Hofman,Mohammad Ikram,Sonia Jain,Ronald Kessler,Maarten Kooyman,James MacKillop,Minna Männikkö,Carlos Morcillo-Suarez,Matthew McQueen,Klaus Schmidt,Melissa Smart,Matthias Sutter,A Thurik,Andre Uitterlinden,Jon White,Harriet Wit,Jian Yang,Lars Bertram,Dorret Boomsma,Tõnu Esko,Ernst Fehr,David Hinds,Magnus Johannesson,Meena Kumari,David Laibson,Patrik Magnusson,Michelle Meyer,Arcadi Navarro,Abraham Palmer,Tune Pers,Danielle Posthuma,Daniel Schunk,Murray Stein,Rauli Svento,Henning Tiemeier,Paul Timmers,Patrick Turley,Robert Ursano,Gert Wagner,James Wilson,Jacob Gratten,James Lee,David Cesarini,Daniel Benjamin,Philipp Koellinger,Jonathan Beauchamp,S. Meddens,Juan González,A.R. Thurik,Richard Linnér,Mary Feitosa,Ilja Demuth,Chia‐Yen Chen,Jaime Derringer,Alison Pattie,Jaakko Kaprio,Sandra Sanchez‐Roige,M. Ikram,Carlos Morcillo-Suárez,Roy Thurik,André Uitterlinden
+105 authors
,Daniëlle Posthuma
Published
Feb 8, 2018
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Abstract

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.

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