SynthesisNature genetics2019
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers, 11 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
392citing papers in PubMed, 11 pooled it
82.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
392 citing papers in PubMed, 11 syntheses or guidelines pooled it, 834 citations in OpenAlex.
- The genetics of cannabis lifetime use.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Pooled it
- Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking.Nature communications · 2025Pooled it
- Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids.Translational psychiatry · 2025Pooled it
- A systematic review and meta-analyses of the temporal stability and convergent validity of risk preference measures.Nature human behaviour · 2025Pooled it
- Exploring risk factors for endocrine-related immune-related adverse events: Insights from meta-analysis and Mendelian randomization.Human vaccines & immunotherapeutics · 2024Pooled it
- Genome-Wide Search for Nonadditive Allele Effects IdentifiesJournal of the American Heart Association · 2024Pooled it
- Associations between genetically predicted concentrations of plasma proteins and the risk of prostate cancer.BMC cancer · 2024Pooled it
- GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.The American journal of psychiatry · 2023Pooled it
- Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies.BMC medicine · 2023Pooled it
- Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure.Nature communications · 2023Pooled it
- Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses.Nature medicine · 2023Pooled it
- Rethinking yield stability through phenotypic plasticity and its link to modern statistical methods.Journal of experimental botany · 2026Review
- Perceived Stress and Disordered Eating Behaviors in Emerging Adulthood: A Multidimensional Pilot Study of Dietary and Genetic Factors.Diseases (Basel, Switzerland) · 2026Article
- Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.Research square · 2026Article
- Article
- Neuroinflammation and depression: immune-brain interface mechanisms, biomarker stratification, and therapeutic strategies.Translational psychiatry · 2026Review
- Genome-wide association study of cocaine self-administration behavior in Heterogeneous Stock rats.Nature communications · 2026Article
- Living happily ever after: longitudinal insights into enduring mental health and wellbeing.Social psychiatry and psychiatric epidemiology · 2026Article
- Causal relationship between tinnitus and 8 psychiatric phenotypes: a Mendelian randomization study.European archives of psychiatry and clinical neuroscience · 2026Article
- Genetic mapping in collaborative cross mouse strains identifies loci that affect initial sensitivity to cocaine.Psychopharmacology · 2026Article
332 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
96 authors at 20 institutions in 15 countries.
Richard Karlsson LinnérDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands. r.karlssonlinner@vu.nl.ORCID http://orcid.org/0000-0001-7839-2858
Pietro BiroliDepartment of Economics, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-5033-4688
Edward KongDepartment of Economics, Harvard University, Cambridge, MA, USA.
S Fleur W MeddensDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
Robbee WedowStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3108-7087
Mark Alan FontanaCenter for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA.
Maël LebretonAmsterdam School of Economics, University of Amsterdam, Amsterdam, the Netherlands.
Stephen P TinoDepartment of Economics, University of Toronto, Toronto, Ontario, Canada.
Abdel AbdellaouiBiological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Anke R HammerschlagDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-4847-4814
Michel G NivardBiological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2015-1888
Aysu OkbayDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-5170-7781
Cornelius A RietveldErasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-4053-1861
Pascal N TimshelNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Maciej TrzaskowskiInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Ronald de VlamingDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-6416-6067
Christian L ZündDepartment of Economics, University of Zurich, Zurich, Switzerland.
Yanchun BaoInstitute for Social and Economic Research, University of Essex, Colchester, UK.ORCID http://orcid.org/0000-0002-6102-5098
Laura BuzduganSeminar for Statistics, Department of Mathematics, ETH Zurich, Zurich, Switzerland.
Ann H CaplinStuyvesant High School, New York, NY, USA.
Chia-Yen ChenStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9548-5597
Peter EibichNuffield Department of Population Health, University of Oxford, Oxford, UK.
Pierre FontanillasResearch, 23andMe, Inc., Mountain View, CA, USA.ORCID http://orcid.org/0000-0002-8944-4454
Juan R GonzalezBarcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
Peter K JoshiCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Ville KarhunenCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
Aaron KleinmanResearch, 23andMe, Inc., Mountain View, CA, USA.
Remy Z LevinDepartment of Economics, University of California San Diego, La Jolla, CA, USA.
Christina M LillGenetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-2805-1307
Gerardus A MeddensTeam Loyalty BV, Hoofddorp, the Netherlands.
Gerard MuntanéDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.ORCID http://orcid.org/0000-0003-1541-8365
Sandra Sanchez-RoigeDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Frank J van RooijDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Erdogan TaskesenDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
Yang WuInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.ORCID http://orcid.org/0000-0002-0128-7280
Futao ZhangInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
23and Me Research Team
eQTLgen Consortium
International Cannabis Consortium
Social Science Genetic Association Consortium
Adam AutonResearch, 23andMe, Inc., Mountain View, CA, USA.
Jason D BoardmanInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
David W ClarkCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Andrew ConlinDepartment of Economics and Finance, Oulu Business School, University of Oulu, Oulu, Finland.
Conor C DolanBiological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Urs FischbacherDepartment of Economics, University of Konstanz, Konstanz, Germany.ORCID http://orcid.org/0000-0002-5115-8815
Patrick J F GroenenErasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
Kathleen Mullan HarrisDepartment of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gregor HaslerUnit of Psychiatry Research, University of Fribourg, Fribourg, Switzerland.
Albert HofmanDepartment of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Mohammad A IkramDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-0372-8585
Sonia JainFamily Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-8949-2587
Ronald C KesslerDepartment of Health Care Policy, Harvard Medical School, Boston, MA, USA.
Maarten KooymanSURFsara, Amsterdam, the Netherlands.
James MacKillopPeter Boris Centre for Addictions Research, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0003-4118-9500
Minna MännikköCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
Carlos Morcillo-SuarezDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Matthew B McQueenDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Klaus M SchmidtDepartment of Economics, University of Munich, Munich, Germany.
Melissa C SmartInstitute for Social and Economic Research, University of Essex, Colchester, UK.
Matthias SutterDepartment of Economics, University of Cologne, Cologne, Germany.
A Roy ThurikErasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-0242-6908
André G UitterlindenDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands.
Jon WhiteUCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.
Harriet de WitPsychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Jian YangInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.ORCID http://orcid.org/0000-0003-2001-2474
Lars BertramGenetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
Dorret I BoomsmaBiological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, Estonia.
Ernst FehrDepartment of Economics, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-6325-7821
David A HindsResearch, 23andMe, Inc., Mountain View, CA, USA.ORCID http://orcid.org/0000-0002-4911-803X
Magnus JohannessonDepartment of Economics, Stockholm School of Economics, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8759-6393
Meena KumariInstitute for Social and Economic Research, University of Essex, Colchester, UK.
David LaibsonDepartment of Economics, Harvard University, Cambridge, MA, USA.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7315-7899
Michelle N MeyerCenter for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA.
Arcadi NavarroDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Tune H PersNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Danielle PosthumaDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-7582-2365
Daniel SchunkDepartment of Economics, Johannes Gutenberg University, Mainz, Germany.
Murray B SteinDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9564-2871
Rauli SventoDepartment of Economics and Finance, Oulu Business School, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0002-0295-7354
Henning TiemeierDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-4395-1397
Paul R H J TimmersCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.ORCID http://orcid.org/0000-0002-5197-1267
Patrick TurleyStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Robert J UrsanoDepartment of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Gert G WagnerSocio-Economic Panel Study, DIW Berlin, Berlin, Germany.
James F WilsonCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.ORCID http://orcid.org/0000-0001-5751-9178
Jacob GrattenInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
James J LeeDepartment of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-6547-5128
David CesariniDepartment of Economics, New York University, New York, NY, USA.
Daniel J BenjaminBehavioral and Health Genomics Center, Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-2642-5416
Philipp D KoellingerDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
Jonathan P BeauchampDepartment of Economics, University of Toronto, Toronto, Ontario, Canada. jonathan.pierre.beauchamp@gmail.com.ORCID http://orcid.org/0000-0002-4935-4016
Amsterdam Neuroscience · NLUniversity of California San Diego · US23andMe (United States) · USErasmus MC · NLHarvard University · USThe University of Queensland · AUUniversity of Oulu · FIUniversity of Zurich · CHVrije Universiteit Amsterdam · NLBroad Institute · USCentre for Global Health Research · CAGerman Institute for Economic Research · DEUniversitat Pompeu Fabra · ESUniversity of Essex · GBKarolinska Institutet · SEStatens Serum Institut · DKUniversity of Colorado Boulder · USUniversity of Toronto · CAErasmus University Rotterdam · NLGeisinger Health System · US
Funding
Wave IV Data CollectionP01HD031921 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HARRIS, KATHLEEN MULLAN · 1994 to 2020
$86.1MUnderstanding and Improving Healthcare Decision-Making and Outcomes for People Living with Alzheimer's Disease and Related DementiasP01AG005842 · NIA · NATIONAL BUREAU OF ECONOMIC RESEARCH · PI KOSALI ILAYPERUMA SIMON · 1986 to 2026
$56.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MNBER Center for Aging and Health Research-Post COVID-19 Experiences Among Adults with ADRDP30AG012810 · NIA · NATIONAL BUREAU OF ECONOMIC RESEARCH · PI DAVID M CUTLER, Karen Ellen Joynt Maddox · 1999 to 2026
$24.6MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MNBER Training Program in Aging and Health EconomicsT32AG000186 · NIA · NATIONAL BUREAU OF ECONOMIC RESEARCH · PI CUTLER, DAVID M, FINKELSTEIN, AMY N. · 1989 to 2024
$9.6MEpidemiologic Study of Impaired Decision-Making in Preclinical Alzheimer's DiseasR01AG033678 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BOYLE, PATRICIA A · 2009 to 2025
$7.8MUniversity of Colorado Population CenterP2CHD066613 · NICHD · UNIVERSITY OF COLORADO · PI JANE A MENKEN · 2015 to 2026
$3.7MGenome-Wide Analyses of Health and Well-Being PhenotypesR01AG042568 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BENJAMIN, DANIEL J · 2015 to 2021
$2.8MGenome-Wide Analyses of Health and Well-Being PhenotypesR56AG042568 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BENJAMIN, DANIEL J · 2018 to 2018
$803kResearch Tools to Enable Widespread Access and Use of Add Health GWAS DataR03HD097630 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AVERY, CHRISTY LEIGH, HARRIS, KATHLEEN MULLAN · 2018 to 2019
$156kBiotechnology and Biological Sciences Research Council BB/F019394/1Biotechnology and Biological Sciences Research Council BB/F022441/1Cancer Research UK 10119Medical Research Council G0100594Medical Research Council G0600237Medical Research Council G0901461Medical Research Council G1001799Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_12013/4Medical Research Council MR/K026992/1Medical Research Council MR/N01104X/2NIA NIH HHS P01 AG005842NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012810NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG033678NIA NIH HHS R01 AG042568NIA NIH HHS R56 AG042568NIA NIH HHS T32 AG000186NICHD NIH HHS P01 HD031921NICHD NIH HHS P2C HD066613NICHD NIH HHS R03 HD097630Wellcome Trust 208806/Z/17/Z
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.
Indexed as
BehaviorCase-Control StudiesFemaleGenetic LociGenetic Predisposition to DiseaseGenetics, BehavioralGenome-Wide Association StudyGenotypeHumansMalePolymorphism, Single Nucleotide
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