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

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

VU University Amsterdam
University of Zurich
Harvard University
Broad Institute of MIT and Harvard
Center for the Advancement of Value in Musculoskeletal Care
University of Amsterdam
University of Toronto
Erasmus University Rotterdam
University of Copenhagen
1] The University of Queensland
University of Essex
Seminar for Statistics
Stuyvesant High School, New York, United States
University of Oxford
Research
Barcelona Institute for Global Health (ISGlobal)
University of Edinburgh
University of Oulu
University of California San Diego
University of Lübeck
Team Loyalty BV, Hoofddorp, Netherlands
Departament de Ciències Experimentals i de la Salut
Erasmus Medical Center
University of Colorado Boulder
Department of Biological Psychology
University of Konstanz
University of North Carolina at Chapel Hill
University of Fribourg
Harvard T.H. Chan School of Public Health
Karolinska Institutet
Harvard Medical School
SURFsara
Pediatric OCD Consultation Team, Anxiety Treatment and Research Centre, St. Joseph's Healthcare, McMaster University, 100 West 5th Street, Hamilton, ON, Canada L8N 3K7.
Technical University of Munich
University of Cologne
Montpellier Business School
Department of Internal Medicine
University College London
University of Chicago
University of Tartu
Stockholm School of Economics
Center for Translational Bioethics and Health Care Policy
Johannes Gutenberg-University
Uniformed Services University of the Health Sciences
German Socio-Economic Panel Study Department
University of Minnesota Twin Cities
New York University
University of Southern California
Vrije Universiteit (VU) Amsterdam and VU Medical Center
Broad Institute
Hospital for Special Surgery - New York
Cornell University
Statens Serum Institut
University of Queensland
Swiss Federal Institute of Technology Zurich
Oxford University Children's Hospital
German Institute for Economic Research
Max Planck Institute for Demographic Research
23andMe Inc.
Centre for Research in Environmental Epidemiology (CREAL)
Pompeu Fabra University
CIBER - Center for Biomedical Research Network
University of California at San Diego
Universidad Rovira i Virgili
Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Reus, Spain
University of Bristol
GGZ InGeest, Amsterdam, Netherlands
Department of Psychiatry
VA Boston Healthcare System
Erasmus MC University Medical Center Rotterdam
Department of Child and Adolescent Psychiatry/Psychology
Massachusetts General Hospital
Usher Institute of Population Health Sciences and Informatics

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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.

Original language	English
Pages (from-to)	245-257
Number of pages	13
Journal	Nature genetics
Volume	51
Issue number	2
Early online date	2019
DOIs	https://doi.org/10.1038/s41588-018-0309-3
Publication status	Published - 1 Feb 2019

Keywords

Behavior/physiology
Case-Control Studies
Female
Genetic Loci/genetics
Genetic Predisposition to Disease/genetics
Genetics, Behavioral/methods
Genome-Wide Association Study/methods
Genotype
Humans
Male
Polymorphism, Single Nucleotide/genetics

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10.1038/s41588-018-0309-3

Genome-wide-association-analyses-of-risk-tolerance-and-risky-behaviors-in-over-1-million-individuals-identify-hundreds-o.pdfFinal published version, 2.07 MBLicence: Taverne

https://pmc.ncbi.nlm.nih.gov/articles/PMC6713272/Licence: Unspecified

Cite this

@article{7af50716298e4f2c9e33323cdb479334,

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 ([Formula: see text] \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.",

keywords = "Behavior/physiology, Case-Control Studies, Female, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genetics, Behavioral/methods, Genome-Wide Association Study/methods, Genotype, Humans, Male, Polymorphism, Single Nucleotide/genetics",

author = "\{Karlsson Linn{\'e}r\}, Richard and Pietro Biroli and \{23and Me Research Team\} 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 Chia-Yen Chen 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 Adam Auton and Boardman, \{Jason D\} and Clark, \{David W\} and Andrew Conlin and Dolan, \{Conor C\} and Urs Fischbacher and Groenen, \{Patrick J F\} and Harris, \{Kathleen Mullan\} and Gregor Hasler and Albert Hofman and Ikram, \{Mohammad A\} and Sonia Jain and Robert Karlsson and Kessler, \{Ronald C\} and Maarten Kooyman and James MacKillop and Minna M{\"a}nnikk{\"o} and Carlos Morcillo-Suarez and McQueen, \{Matthew B\} and Schmidt, \{Klaus M\} and Smart, \{Melissa C\} and Matthias Sutter and Thurik, \{A Roy\} and Uitterlinden, \{Andr{\'e} G\} and Jon White and Wit, \{Harriet de\} and Jian Yang and Lars Bertram and Boomsma, \{Dorret I\} and T{\~o}nu Esko and Ernst Fehr and Hinds, \{David A\} and Magnus Johannesson and Meena Kumari and David Laibson and Magnusson, \{Patrik K E\} and Meyer, \{Michelle N\} and Arcadi Navarro and Palmer, \{Abraham A\} and Pers, \{Tune H\} and Danielle Posthuma and Daniel Schunk and Stein, \{Murray B\} and Rauli Svento and Henning Tiemeier and Timmers, \{Paul R H J\} and Patrick Turley and Ursano, \{Robert J\} and Wagner, \{Gert G\} and Wilson, \{James F\} and Jacob Gratten and Lee, \{James J\} and David Cesarini and Benjamin, \{Daniel J\} and Koellinger, \{Philipp D\} and Beauchamp, \{Jonathan P\} and Rick Jansen and Brenda Penninx and Peyrot, \{Wouter J.\} and Evans, \{David M.\} and Yuri Milaneschi",

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 Publishing Group",

number = "2",

}

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 - Karlsson Linnér, Richard

AU - Biroli, Pietro

AU - 23and Me Research Team

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 - Auton, Adam

AU - Boardman, Jason D

AU - Clark, David W

AU - Conlin, Andrew

AU - Dolan, Conor C

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

AU - Kooyman, Maarten

AU - MacKillop, James

AU - Männikkö, Minna

AU - Morcillo-Suarez, Carlos

AU - McQueen, Matthew B

AU - Schmidt, Klaus M

AU - Smart, Melissa C

AU - Sutter, Matthias

AU - Thurik, A Roy

AU - Uitterlinden, André G

AU - White, Jon

AU - Wit, Harriet de

AU - Yang, Jian

AU - Bertram, Lars

AU - Boomsma, Dorret I

AU - Esko, Tõnu

AU - Fehr, Ernst

AU - Hinds, David A

AU - Johannesson, Magnus

AU - Kumari, Meena

AU - Laibson, David

AU - Magnusson, Patrik K E

AU - Meyer, Michelle N

AU - Navarro, Arcadi

AU - Palmer, Abraham A

AU - Pers, Tune H

AU - Posthuma, Danielle

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 - Gratten, Jacob

AU - Lee, James J

AU - Cesarini, David

AU - Benjamin, Daniel J

AU - Koellinger, Philipp D

AU - Beauchamp, Jonathan P

AU - Jansen, Rick

AU - Penninx, Brenda

AU - Peyrot, Wouter J.

AU - Evans, David M.

AU - Milaneschi, Yuri

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 ([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.

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 ([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.

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

UR - https://www.ncbi.nlm.nih.gov/pubmed/30643258

U2 - 10.1038/s41588-018-0309-3

DO - 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 -

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

Abstract

Keywords

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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

Abstract

Keywords

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