TY - JOUR
T1 - Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
AU - Social Science Genetic Association Consortium
AU - 23and Me Research Team
AU - eQTLGen Consortium
AU - International Cannabis Consortium
AU - Karlsson Linnér, Richard
AU - Biroli, Pietro
AU - Kong, Edward
AU - Meddens, S. Fleur W.
AU - Wedow, Robbee
AU - Fontana, Mark Alan
AU - Lebreton, Maël
AU - Tino, Stephen P.
AU - Abdellaoui, Abdel
AU - Hammerschlag, Anke R.
AU - Nivard, Michel G.
AU - Okbay, Aysu
AU - Rietveld, Cornelius A.
AU - Timshel, Pascal N.
AU - Trzaskowski, Maciej
AU - Vlaming, Ronald de
AU - Zünd, Christian L.
AU - Bao, Yanchun
AU - Buzdugan, Laura
AU - Caplin, Ann H.
AU - Chen, Chia Yen
AU - Eibich, Peter
AU - Fontanillas, Pierre
AU - Gonzalez, Juan R.
AU - Joshi, Peter K.
AU - Karhunen, Ville
AU - Kleinman, Aaron
AU - Levin, Remy Z.
AU - Lill, Christina M.
AU - Meddens, Gerardus A.
AU - Muntané, Gerard
AU - Sanchez-Roige, Sandra
AU - Rooij, Frank J.van
AU - Taskesen, Erdogan
AU - Wu, Yang
AU - Zhang, Futao
AU - Agee, Michelle
AU - Alipanahi, Babak
AU - Bell, Robert K.
AU - Bryc, Katarzyna
AU - Boomsma, Dorret I.
AU - Nivard, Michel G.
AU - Okbay, Aysu
AU - de Vlaming, Ronald
AU - de Leeuw, Christiaan
AU - Hottenga, Jouke Jan
AU - Willemsen, Gonneke
AU - Koellinger, Philipp D.
AU - Posthuma, Danielle
AU - Koellinger, Philipp D.
AU - Jansen, Rick
AU - Penninx, Brenda
AU - Peyrot, Wouter J.
AU - Evans, David M.
AU - Milaneschi, Yuri
AU - Schunk, Daniel
AU - Stein, Murray B
AU - Svento, Rauli
AU - Tiemeier, Henning
AU - Timmers, Paul R. H. J.
AU - Turley, Patrick
AU - Ursano, Robert J.
AU - Wagner, Gert G.
AU - Wilson, James F.
AU - Auton, Adam
AU - Boardman, Jason D
AU - Clark, David W
AU - Conlin, Andrew
AU - Fischbacher, Urs
AU - Groenen, Patrick J F
AU - Harris, Kathleen Mullan
AU - Hasler, Gregor
AU - Hofman, Albert
AU - Ikram, Mohammad A
AU - Jain, Sonia
AU - Karlsson, Robert
AU - Kessler, Ronald C
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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 (∣r̂ 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.
AB - 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 (∣r̂ 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.
KW - Behavior/physiology
KW - Case-Control Studies
KW - Female
KW - Genetic Loci/genetics
KW - Genetic Predisposition to Disease/genetics
KW - Genetics, Behavioral/methods
KW - Genome-Wide Association Study/methods
KW - Genotype
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide/genetics
UR - http://www.scopus.com/inward/record.url?scp=85060083196&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060083196&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060083196&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30643258
U2 - https://doi.org/10.1038/s41588-018-0309-3
DO - https://doi.org/10.1038/s41588-018-0309-3
M3 - Article
C2 - 30643258
SN - 1061-4036
VL - 51
SP - 245
EP - 257
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -