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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.

Journal article
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 C 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
Jonathan P Beauchamp
Bo Jacobsson
Daniel J. Benjamin
Published in Nature genetics
Volume 51
Pages 245–257
ISSN 1546-1718
Publication year 2019
Published at Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 245–257
Language en
Links dx.doi.org/10.1038/s41588-018-0309-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Obstetrics, Gynecology and Reproductive Medicine, Obstetrics and women's diseases, Obstetrics and gynaecology, Clinical Medicine

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.

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