Format

Send to

Choose Destination
Nat Genet. 2019 Feb;51(2):245-257. doi: 10.1038/s41588-018-0309-3. Epub 2019 Jan 14.

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

Collaborators (352)

Agee M, Alipanahi B, Bell RK, Bryc K, Elson SL, Furlotte NA, Huber KE, Litterman NK, McCreight JC, McIntyre MH, Mountain JL, Northover CAM, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Tung JY, Vacic V, Wilson CH, Agbessi M, Ahsan H, Alves I, Andiappan A, Awadalla P, Battle A, Beutner F, Jan Bonder M, Boomsma DI, Christiansen M, Claringbould A, Deelen P, Esko T, Favé MJ, Franke L, Frayling T, Gharib SA, Gibson G, Heijmans B, Hemani G, Jansen R, Kähönen M, Kalnapenkis A, Kasela S, Kettunen J, Kim Y, Kirsten H, Kovacs P, Krohn K, Kronberg-Guzman J, Kukushkina V, Kutalik Z, Lee B, Lehtimäki T, Loeffler M, Marigorta UM, Metspalu A, Milani L, Montgomery GW, Müller-Nurasyid M, Nauck M, Nivard MG, Penninx B, Perola M, Pervjakova N, Pierce B, Powell J, Prokisch H, Psaty BM, Raitakari O, Ring S, Ripatti S, Rotzchke O, Rüeger S, Saha A, Scholz M, Schramm K, Seppälä I, Stumvoll M, Sullivan P, Hoen PT, Teumer A, Thiery J, Tong L, Tönjes A, Dongen JV, Meurs JV, Verlouw J, Visscher PM, Völker U, Võsa U, Westra HJ, Yaghootkar H, Yang J, Zeng B, Zhang F, Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA, Turley P, Chen GB, Emilsson V, Meddens SFW, Oskarsson S, Pickrell JK, Thom K, Timshel P, de Vlaming R, Abdellaoui A, Ahluwalia TS, Bacelis J, Baumbach C, Bjornsdottir G, Brandsma JH, Concas MP, Derringer J, Furlotte NA, Galesloot TE, Girotto G, Gupta R, Hall LM, Harris SE, Hofer E, Horikoshi M, Huffman JE, Kaasik K, Kalafati IP, Karlsson R, Kong A, Lahti J, Lee SJV, de Leeuw C, Lind PA, Lindgren KO, Liu T, Mangino M, Marten J, Mihailov E, Miller MB, Most PJV, Oldmeadow C, Payton A, Pervjakova N, Peyrot WJ, Qian Y, Raitakari O, Rueedi R, Salvi E, Schmidt B, Schraut KE, Shi J, Smith AV, Poot RA, Pourcain BS, Teumer A, Thorleifsson G, Verweij N, Vuckovic D, Wellmann J, Westra HJ, Yang J, Zhao W, Zhu Z, Alizadeh BZ, Amin N, Bakshi A, Baumeister SE, Biino G, Bønnelykke K, Boyle PA, Campbell H, Cappuccio FP, Davies G, De Neve JE, Deloukas P, Demuth I, Ding J, Eibich P, Eisele L, Eklund N, Evans DM, Faul JD, Feitosa MF, Forstner AJ, Gandin I, Gunnarsson B, Halldórsson BV, Harris TB, Heath AC, Hocking LJ, Holliday EG, Homuth G, Horan MA, Hottenga JJ, de Jager PL, Joshi PK, Jugessur A, Kaakinen MA, Kähönen M, Kanoni S, Keltigangas-Järvinen L, Kiemeney LALM, Kolcic I, Koskinen S, Kraja AT, Kroh M, Kutalik Z, Latvala A, Launer LJ, Lebreton MP, Levinson DF, Lichtenstein P, Lichtner P, Liewald DCM, Loukola A, Madden PA, Mägi R, Mäki-Opas T, Marioni RE, Marques-Vidal P, Meddens GA, McMahon G, Meisinger C, Meitinger T, Milaneschi Y, Milani L, Montgomery GW, Myhre R, Nelson CP, Nyholt DR, Ollier WER, Palotie A, Paternoster L, Pedersen NL, Petrovic KE, Porteous DJ, Räikkönen K, Ring SM, Robino A, Rostapshova O, Rudan I, Rustichini A, Salomaa V, Sanders AR, Sarin AP, Schmidt H, Scott RJ, Smith BH, Smith JA, Staessen JA, Steinhagen-Thiessen E, Strauch K, Terracciano A, Tobin MD, Ulivi S, Vaccargiu S, Quaye L, Rooij FJV, Venturini C, Vinkhuyzen AAE, Völker U, Völzke H, Vonk JM, Vozzi D, Waage J, Ware EB, Willemsen G, Attia JR, Bennett DA, Berger K, Bertram L, Bisgaard H, Boomsma DI, Borecki IB, Bültmann U, Chabris CF, Cucca F, Cusi D, Deary IJ, Dedoussis GV, Duijn CMV, Eriksson JG, Franke B, Franke L, Gasparini P, Gejman PV, Gieger C, Grabe HJ, Gratten J, Groenen PJF, Gudnason V, Harst PV, Hayward C, Hinds DA, Hoffmann W, Hyppönen E, Iacono WG, Jacobsson B, Järvelin MR, Jöckel KH, Kaprio J, Kardia SLR, Lehtimäki T, Lehrer SF, Magnusson PKE, Martin NG, McGue M, Metspalu A, Pendleton N, Penninx B, Perola M, Pirastu N, Pirastu M, Polasek O, Posthuma D, Power C, Province MA, Samani NJ, Schlessinger D, Schmidt R, Sørensen TIA, Spector TD, Stefansson K, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tiemeier H, Tung JY, Uitterlinden AG, Vitart V, Vollenweider P, Weir DR, Wilson JF, Wright AF, Conley DC, Krueger RF, Smith GD, Hofman A, Laibson DI, Medland SE, Meyer MN, Yang J, Johannesson M, Visscher PM, Esko T, Koellinger PD, Cesarini D, Benjamin DJ.

Author information

1
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands. r.karlssonlinner@vu.nl.
2
Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands. r.karlssonlinner@vu.nl.
3
Department of Economics, VU University Amsterdam, Amsterdam, the Netherlands. r.karlssonlinner@vu.nl.
4
Department of Economics, University of Zurich, Zurich, Switzerland.
5
Department of Economics, Harvard University, Cambridge, MA, USA.
6
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
7
Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
8
Department of Economics, VU University Amsterdam, Amsterdam, the Netherlands.
9
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
10
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
11
Analytic Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
12
Department of Sociology, Harvard University, Cambridge, MA, USA.
13
Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA.
14
Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY, USA.
15
Amsterdam School of Economics, University of Amsterdam, Amsterdam, the Netherlands.
16
Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.
17
Department of Economics, University of Toronto, Toronto, Ontario, Canada.
18
Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
19
Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
20
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
21
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
22
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
23
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
24
Institute for Social and Economic Research, University of Essex, Colchester, UK.
25
Seminar for Statistics, Department of Mathematics, ETH Zurich, Zurich, Switzerland.
26
Stuyvesant High School, New York, NY, USA.
27
Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
28
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
29
Socio-Economic Panel Study, DIW Berlin, Berlin, Germany.
30
Max Planck Institute for Demographic Research, Rostock, Germany.
31
Research, 23andMe, Inc., Mountain View, CA, USA.
32
Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
33
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
34
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
35
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
36
Center for Life Course Health Research, University of Oulu, Oulu, Finland.
37
Department of Economics, University of California San Diego, La Jolla, CA, USA.
38
Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
39
Team Loyalty BV, Hoofddorp, the Netherlands.
40
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
41
Research Department, Hospital Universitari Institut Pere Mata, Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
42
Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Reus, Spain.
43
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
44
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
45
Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
46
Department of Sociology, University of Colorado Boulder, Boulder, CO, USA.
47
Department of Economics and Finance, Oulu Business School, University of Oulu, Oulu, Finland.
48
Department of Economics, University of Konstanz, Konstanz, Germany.
49
Thurgau Institute of Economics, Kreuzlingen, Switzerland.
50
Department of Econometrics, Erasmus University Rotterdam, Rotterdam, Rotterdam, the Netherlands.
51
Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
52
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
53
Unit of Psychiatry Research, University of Fribourg, Fribourg, Switzerland.
54
Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
55
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
56
Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
57
SURFsara, Amsterdam, the Netherlands.
58
Peter Boris Centre for Addictions Research, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
59
Homewood Research Institute, Guelph, Ontario, Canada.
60
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
61
Department of Economics, University of Munich, Munich, Germany.
62
Department of Economics, University of Cologne, Cologne, Germany.
63
Experimental Economics Group, Max Planck Institute for Research into Collective Goods, Bonn, Germany.
64
Department of Public Finance, University of Innsbruck, Innsbruck, Austria.
65
Montpellier Business School, Montpellier, France.
66
Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands.
67
UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.
68
Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
69
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
70
Dept of Psychology, University of Olso, Oslo, Norway.
71
School of Public Health, Imperial College London, London, UK.
72
Estonian Genome Center, University of Tartu, Tartu, Estonia.
73
Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
74
Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA.
75
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
76
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
77
Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
78
Department of Clinical Genetics, VU Medical Centre, Amsterdam, the Netherlands.
79
Department of Economics, Johannes Gutenberg University, Mainz, Germany.
80
Behavioral and Health Genomics Center, Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
81
Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
82
Max Planck Institute for Human Development, Berlin, Germany.
83
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
84
Mater Medical Research Institute, Translational Research Institute, Brisbane, Australia.
85
Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
86
Department of Economics, New York University, New York, NY, USA.
87
Department of Economics, University of Southern California, Los Angeles, CA, USA.
88
National Bureau of Economic Research, Cambridge, MA, USA.
89
German Institute for Economic Research, DIW Berlin, Berlin, Germany.
90
Department of Economics, University of Toronto, Toronto, Ontario, Canada. jonathan.pierre.beauchamp@gmail.com.

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.

PMID:
30643258
DOI:
10.1038/s41588-018-0309-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center