Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

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...

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Autores: Karlsson Linnér, Richard, González, Juan Ramón, Muntané, Gerard, Morcillo Suárez, Carlos, 1969-, Navarro i Cuartiellas, Arcadi, 1969-, Beauchamp, Jonathan P.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/56575
Acceso en línea:http://hdl.handle.net/10230/56575
http://dx.doi.org/10.1038/s41588-018-0309-3
Access Level:acceso abierto
Palabra clave:Behavioural genetics
Genome-wide association studies
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spelling Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influencesKarlsson Linnér, RichardGonzález, Juan RamónMuntané, GerardMorcillo Suárez, Carlos, 1969-Navarro i Cuartiellas, Arcadi, 1969-Beauchamp, Jonathan P.Behavioural geneticsGenome-wide association studiesHumans 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.This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.Nature Research202320232019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/56575http://dx.doi.org/10.1038/s41588-018-0309-3reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNat Genet. 2019;51(2):245-57info:eu-repo/grantAgreement/EC/H2020/647648info:eu-repo/grantAgreement/EC/H2020/647648© Springer Nature Publishing AG. Karlsson Linnér R, Biroli P, Kong E, Meddens SFW, Wedow R, Fontana MA et al. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nat Genet. 2019;51(2):245-57. DOI 10.1038/s41588-018-0309-3 [http://dx.doi.org/10.1038/s41588-018-0309-3]info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/565752026-06-12T07:21:37Z
dc.title.none.fl_str_mv Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
title Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
spellingShingle 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
Behavioural genetics
Genome-wide association studies
title_short Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
title_full Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
title_fullStr Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
title_full_unstemmed Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
title_sort Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
dc.creator.none.fl_str_mv Karlsson Linnér, Richard
González, Juan Ramón
Muntané, Gerard
Morcillo Suárez, Carlos, 1969-
Navarro i Cuartiellas, Arcadi, 1969-
Beauchamp, Jonathan P.
author Karlsson Linnér, Richard
author_facet Karlsson Linnér, Richard
González, Juan Ramón
Muntané, Gerard
Morcillo Suárez, Carlos, 1969-
Navarro i Cuartiellas, Arcadi, 1969-
Beauchamp, Jonathan P.
author_role author
author2 González, Juan Ramón
Muntané, Gerard
Morcillo Suárez, Carlos, 1969-
Navarro i Cuartiellas, Arcadi, 1969-
Beauchamp, Jonathan P.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Behavioural genetics
Genome-wide association studies
topic Behavioural genetics
Genome-wide association studies
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/56575
http://dx.doi.org/10.1038/s41588-018-0309-3
url http://hdl.handle.net/10230/56575
http://dx.doi.org/10.1038/s41588-018-0309-3
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Genet. 2019;51(2):245-57
info:eu-repo/grantAgreement/EC/H2020/647648
info:eu-repo/grantAgreement/EC/H2020/647648
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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