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

23and Me Research Team; eQTLgen Consortium; International Cannabis Consortium; Social Science Genetic Association Consortium

doi:10.1038/s41588-018-0309-3

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

23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Social Science Genetic Association Consortium

497 Citations (Scopus)

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 (∣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.

Original language	English
Journal	Nature Genetics
Volume	51
Issue number	2
Pages (from-to)	245-257
Number of pages	13
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0309-3
Publication status	Published - 01.02.2019

Funding

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.

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SDG 9 Industry, Innovation, and Infrastructure

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10.1038/s41588-018-0309-3

Cite this

@article{f5273f0f3b6c42fc8fd0915b44607870,

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

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∣ \textasciitilde{} 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.",

author = "\{23and Me Research Team\} and \{eQTLgen Consortium\} and \{International Cannabis Consortium\} and \{Social Science Genetic Association Consortium\} and \{Karlsson Linn{\'e}r\}, Richard and Pietro Biroli and Edward Kong and Meddens, \{S. Fleur W.\} and Robbee Wedow and Fontana, \{Mark Alan\} and Ma{\"e}l Lebreton and Tino, \{Stephen P.\} and Abdel Abdellaoui and Hammerschlag, \{Anke R.\} and Nivard, \{Michel G.\} and Aysu Okbay and Rietveld, \{Cornelius A.\} and Timshel, \{Pascal N.\} and Maciej Trzaskowski and Vlaming, \{Ronald de\} and Z{\"u}nd, \{Christian L.\} and Yanchun Bao and Laura Buzdugan and Caplin, \{Ann H.\} and Chen, \{Chia Yen\} and Peter Eibich and Pierre Fontanillas and Gonzalez, \{Juan R.\} and Joshi, \{Peter K.\} and Ville Karhunen and Aaron Kleinman and Levin, \{Remy Z.\} and Lill, \{Christina M.\} and Meddens, \{Gerardus A.\} and Gerard Muntan{\'e} and Sandra Sanchez-Roige and Rooij, \{Frank J.van\} and Erdogan Taskesen and Yang Wu and Futao Zhang and Michelle Agee and Babak Alipanahi and Bell, \{Robert K.\} and Katarzyna Bryc and Elson, \{Sarah L.\} and Furlotte, \{Nicholas A.\} and Huber, \{Karen E.\} and Litterman, \{Nadia K.\} and McCreight, \{Jennifer C.\} and McIntyre, \{Matthew H.\} and Mountain, \{Joanna L.\} and Helena Schmidt and Klaus Berger and Lars Bertram",

note = "Funding Information: 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 S{\"o}derberg 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. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = feb,

day = "1",

doi = "10.1038/s41588-018-0309-3",

language = "English",

volume = "51",

pages = "245--257",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

}

23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium & Social Science Genetic Association Consortium 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 Genetics, vol. 51, no. 2, pp. 245-257. https://doi.org/10.1038/s41588-018-0309-3

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. / 23and Me Research Team; eQTLgen Consortium; International Cannabis Consortium et al.
In: Nature Genetics, Vol. 51, No. 2, 01.02.2019, p. 245-257.

Research output: Journal Articles › Journal articles › Research › peer-review

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 - 23and Me Research Team

AU - eQTLgen Consortium

AU - International Cannabis Consortium

AU - Social Science Genetic Association 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 - Elson, Sarah L.

AU - Furlotte, Nicholas A.

AU - Huber, Karen E.

AU - Litterman, Nadia K.

AU - McCreight, Jennifer C.

AU - McIntyre, Matthew H.

AU - Mountain, Joanna L.

AU - Schmidt, Helena

AU - Berger, Klaus

AU - Bertram, Lars

N1 - Funding Information: 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. Publisher Copyright: © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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.

UR - https://www.scopus.com/pages/publications/85060083196

U2 - 10.1038/s41588-018-0309-3

DO - 10.1038/s41588-018-0309-3

M3 - Journal articles

C2 - 30643258

AN - SCOPUS:85060083196

SN - 1061-4036

VL - 51

SP - 245

EP - 257

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

Funding

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