Article | Published:

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

Nature Geneticsvolume 51pages245257 (2019) | Download Citation

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 (\(\left| {\hat r_{\mathrm{g}}} \right|\) ~ 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.

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Data availability

GWAS summary statistics can be downloaded from http://www.thessgac.org/data. SNP-level summary statistics from analyses based entirely or in part on 23andMe data can only be reported for up to 10,000 SNPs. For general risk tolerance, we provide association results for all SNPs that passed quality-control filters in a GWAS meta-analysis of general risk tolerance that excludes the research participants from 23andMe; we also provide association results from the complete GWAS (which includes data from 23andMe) for all lead SNPs identified in our discovery GWAS and MTAG analysis of general risk tolerance and for the 4,000 most significant SNPs in the meta-analysis of the discovery and replication GWAS of risk tolerance. For adventurousness, we provide association results from the complete GWAS (which includes only data from 23andMe) for all lead SNPs and for the next 4,000 most significant SNPs. For automobile speeding propensity, drinks per week, ever smoker, number of sexual partners, and the first PC of the four risky behaviors, we provide association results from the complete GWAS for all SNPs that passed quality-control filters. Contact information for the cohorts included in this paper can be found in the Supplementary Note.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Dohmen, T. et al. Individual risk attitudes: measurement, determinants, and behavioral consequences. J. Eur. Econ. Assoc. 9, 522–550 (2011).

  2. 2.

    Falk, A., et al. The Nature and Predictive Power of Preferences: Global Evidence (IZA Institute of Labor Economics, 2015).

  3. 3.

    Beauchamp, J. P., Cesarini, D. & Johannesson, M. The psychometric and empirical properties of measures of risk preferences. J. Risk Uncertain. 54, 203–237 (2017).

  4. 4.

    Cesarini, D., Dawes, C. T., Johannesson, M., Lichtenstein, P. & Wallace, B. Genetic variation in preferences for giving and risk taking. Q. J. Econ. 124, 809–842 (2009).

  5. 5.

    Harden, K. P. et al. Beyond dual systems: a genetically-informed, latent factor model of behavioral and self-report measures related to adolescent risk-taking. Dev. Cogn. Neurosci. 25, 221–234 (2017).

  6. 6.

    Hewitt, J. K. Editorial policy on candidate gene association and candidate gene-by-environment interaction studies of complex traits. Behav. Genet. 42, 1–2 (2012).

  7. 7.

    Day, F. R. et al. Physical and neurobehavioral determinants of reproductive onset and success. Nat. Genet. 48, 617–623 (2016).

  8. 8.

    Strawbridge, R. J. et al. Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort. Transl. Psychiatry 8, 1–11 (2018).

  9. 9.

    Bulik-Sullivan, B. K. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015).

  10. 10.

    Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 48, 624–633 (2016).

  11. 11.

    Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291–295 (2015).

  12. 12.

    Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369–375 (2012).

  13. 13.

    Byrnes, J. P., Miller, D. C. & Schafer, W. D. Gender differences in risk taking: a meta-analysis. Psychol. Bull. 125, 367–383 (1999).

  14. 14.

    Croson, R. & Gneezy, U. Gender differences in preferences. J. Econ. Lit. 47, 448–474 (2009).

  15. 15.

    Turley, P. et al. Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat. Genet. 50, 229–237 (2018).

  16. 16.

    Shi, H., Kichaev, G. & Pasaniuc, B. Contrasting the genetic architecture of 30 complex traits from summary association data. Am. J. Hum. Genet. 99, 139–153 (2016).

  17. 17.

    Price, A. L. et al. Long-range LD can confound genome scans in admixed populations. Am. J. Hum. Genet. 83, 132–139 (2008).

  18. 18.

    Berisa, T. & Pickrell, J. K. Approximately independent linkage disequilibrium blocks in human populations. Bioinformatics 32, 283–285 (2016).

  19. 19.

    Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001–D1006 (2014).

  20. 20.

    Einav, B. L., Finkelstein, A., Pascu, I. & Cullen, M. R. How general are risk preferences? Choices under uncertainty in different domains. Am. Econ. Rev. 102, 2606–2638 (2016).

  21. 21.

    Frey, R., Pedroni, A., Mata, R., Rieskamp, J. & Hertwig, R. Risk preference shares the psychometric structure of major psychological traits. Sci. Adv. 3, e1701381 (2017).

  22. 22.

    Weber, E. U., Blais, A. E. & Betz, N. E. A domain-specific risk-attitude scale: measuring risk perceptions and risk behaviors. J. Behav. Decis. Mak. 15, 263–290 (2002).

  23. 23.

    Hanoch, Y., Johnson, J. G. & Wilke, A. Domain specificity in experimental measures and participant recruitment: an application to risk-taking behavior. Psychol. Sci. 17, 300–304 (2006).

  24. 24.

    Stringer, S. et al. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32,330 subjects from the International Cannabis Consortium. Transl. Psychiatry 6, e769 (2016).

  25. 25.

    Becker, A., Deckers, T., Dohmen, T., Falk, A. & Kosse, F. The relationship between economic preferences and psychological personality measures. Annu. Rev. Econ. 4, 453–478 (2012).

  26. 26.

    Krueger, R. F. et al. Etiologic connections among substance dependence, antisocial behavior and personality: modeling the externalizing spectrum. J. Abnorm. Psychol. 111, 411–424 (2002).

  27. 27.

    Vilhjálmsson, B. J. et al. Modeling linkage disequilibrium increases accuracy of polygenic risk scores. Am. J. Hum. Genet. 97, 576–592 (2015).

  28. 28.

    Daetwyler, H. D., Villanueva, B. & Woolliams, J. A. Accuracy of predicting the genetic risk of disease using a genome-wide approach. PLoS ONE 3, e3395 (2008).

  29. 29.

    de Vlaming, R. et al. Meta-GWAS Accuracy and Power (MetaGAP) calculator shows that hiding heritability is partially due to imperfect genetic correlations across studies. PLoS Genet. 13, e1006495 (2017).

  30. 30.

    de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11, 1–19 (2015).

  31. 31.

    Fehrmann, R. S. N. et al. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat. Genet. 47, 115–125 (2015).

  32. 32.

    Pers, T. H. et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat. Commun. 6, 5890 (2015).

  33. 33.

    Petroff, O. A. C. GABA and glutamate in the human brain. Neurosci. 8, 562–573 (2002).

  34. 34.

    Lee, J. et al. Gene discovery and polygenic prediction from a 1.1-million-person GWAS of educational attainment. Nat. Genet. 50, 1112–1121 (2018).

  35. 35.

    Ripke, S. et al. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).

  36. 36.

    Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018).

  37. 37.

    Haber, S. N. & Knutson, B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26 (2010).

  38. 38.

    Tobler, P. N. & Weber, E. U. in Neuroeconomics 149–172 (Elsevier, Amsterdam, 2014).

  39. 39.

    Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 1228–1235 (2015).

  40. 40.

    Sahm, C. R. How much does risk tolerance change? Q. J. Finance 2, 1250020 (2012).

  41. 41.

    Malmendier, U. & Nagel, S. Depression babies: do macroeconomic experiences affect risk taking? Q. J. Econ. 126, 373–416 (2011).

  42. 42.

    Frey, B. J. & Dueck, D. Clustering by passing messages between data points. Science 315, 972–976 (2007).

  43. 43.

    Furberg, H. et al. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat. Genet. 42, 441–447 (2010).

  44. 44.

    Winkler, T. W. et al. Quality control and conduct of genome-wide association meta-analyses. Nat. Protoc. 9, 1192–1212 (2014).

  45. 45.

    Ripke, S. et al. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).

  46. 46.

    Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539–542 (2016).

  47. 47.

    Shi, H., Kichaev, G. & Pasaniuc, B. Contrasting the genetic architecture of 30 complex traits from summary association data. Am. J. Hum. Genet. 99, 139–153 (2016).

  48. 48.

    Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).

  49. 49.

    Finucane, H. K. et al. Partitioning heritability by functional category using GWAS summary statistics. Nat. Genet. 47, 1228–1235 (2015).

  50. 50.

    Demontis, D. et al. Discovery of the first genome-wide significant risk loci for ADHD. Preprint at https://doi.org/10.1101/145581 (2017).

  51. 51.

    Stringer, S. et al. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Transl. Psychiatry 6, e769 (2016).

  52. 52.

    Vilhjálmsson, B. J. et al. Modeling linkage disequilibrium increases accuracy of polygenic risk scores. Am. J. Hum. Genet. 97, 576–592 (2015).

  53. 53.

    Dudbridge, F. Power and predictive accuracy of polygenic risk scores. PLoS Genet. 9, e1003348 (2013).

  54. 54.

    Purcell, S. M. et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752 (2009).

  55. 55.

    Buchanan, C. C., Torstenson, E. S., Bush, W. S. & Ritchie, M. D. A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data. J. Am. Med. Informatics Assoc. 19, 289–294 (2012).

  56. 56.

    Zhu, Z. et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet. 48, 481–487 (2016).

Download references

Acknowledgements

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.

Author information

Author notes

  1. These authors contributed equally: Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S. Fleur W. Meddens, Robbee Wedow.

  2. These authors jointly supervised this work: Daniel J. Benjamin, Philipp D. Koellinger, Jonathan P. Beauchamp.

  3. A list of members and affiliations appears in the Supplementary Note.

Affiliations

  1. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands

    • Richard Karlsson Linnér
    • , S. Fleur W. Meddens
    • , Anke R. Hammerschlag
    • , Aysu Okbay
    • , Ronald de Vlaming
    • , Erdogan Taskesen
    • , Aysu Okbay
    • , S. Fleur W. Meddens
    • , Ronald de Vlaming
    • , Christiaan de Leeuw
    • , Danielle Posthuma
    • , Philipp D. Koellinger
    • , Danielle Posthuma
    •  & Philipp D. Koellinger
  2. Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands

    • Richard Karlsson Linnér
    • , S. Fleur W. Meddens
    • , Cornelius A. Rietveld
    • , Ronald de Vlaming
    • , Cornelius A. Rietveld
    • , S. Fleur W. Meddens
    • , Ronald de Vlaming
    • , Patrick J. F. Groenen
    • , A. Roy Thurik
    • , Patrick J. F. Groenen
    •  & A. Roy Thurik
  3. Department of Economics, VU University Amsterdam, Amsterdam, the Netherlands

    • Richard Karlsson Linnér
    • , S. Fleur W. Meddens
    • , Aysu Okbay
    • , Ronald de Vlaming
    • , Aysu Okbay
    • , S. Fleur W. Meddens
    • , Ronald de Vlaming
    • , Philipp D. Koellinger
    •  & Philipp D. Koellinger
  4. Department of Economics, University of Zurich, Zurich, Switzerland

    • Pietro Biroli
    •  & Christian L. Zünd
  5. Department of Economics, Harvard University, Cambridge, MA, USA

    • Edward Kong
    • , Olga Rostapshova
    • , David I. Laibson
    •  & David Laibson
  6. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Robbee Wedow
    • , Chia-Yen Chen
    • , Patrick Turley
    • , Aarno Palotie
    •  & Patrick Turley
  7. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    • Robbee Wedow
    • , Albert Hofman
    •  & Albert Hofman
  8. Analytic Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    • Robbee Wedow
    • , Chia-Yen Chen
    • , Patrick Turley
    •  & Patrick Turley
  9. Department of Sociology, Harvard University, Cambridge, MA, USA

    • Robbee Wedow
  10. Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA

    • Mark Alan Fontana
    •  & Mark Alan Fontana
  11. Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY, USA

    • Mark Alan Fontana
    •  & Mark Alan Fontana
  12. Amsterdam School of Economics, University of Amsterdam, Amsterdam, the Netherlands

    • Maël Lebreton
    •  & Maël P. Lebreton
  13. Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands

    • Maël Lebreton
    •  & Maël P. Lebreton
  14. Department of Economics, University of Toronto, Toronto, Ontario, Canada

    • Stephen P. Tino
    • , Jonathan P. Beauchamp
    •  & Jonathan P. Beauchamp
  15. Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    • Abdel Abdellaoui
    • , Michel G. Nivard
    • , Dorret I. Boomsma
    • , Abdel Abdellaoui
    • , Jouke-Jan Hottenga
    • , Gonneke Willemsen
    • , Dorret I. Boomsma
    • , Conor C. Dolan
    •  & Dorret I. Boomsma
  16. Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands

    • Cornelius A. Rietveld
    •  & Cornelius A. Rietveld
  17. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

    • Cornelius A. Rietveld
    • , Frank J. van Rooij
    • , Cornelius A. Rietveld
    • , Sven J. van der Lee
    • , Najaf Amin
    • , Frank J. van Rooij
    • , Cornelia M. van Duijn
    • , Henning Tiemeier
    • , Albert Hofman
    • , Albert Hofman
    • , Mohammad A. Ikram
    •  & Henning Tiemeier
  18. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

    • Pascal N. Timshel
    • , Tune H. Pers
    • , Pascal Timshel
    • , Tarunveer S. Ahluwalia
    • , Thorkild I. A. Sørensen
    •  & Tune H. Pers
  19. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    • Pascal N. Timshel
    • , Tune H. Pers
    • , Pascal Timshel
    •  & Tune H. Pers
  20. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

    • Maciej Trzaskowski
    • , Yang Wu
    • , Futao Zhang
    • , Grant W. Montgomery
    • , Peter M. Visscher
    • , Jian Yang
    • , Futao Zhang
    • , Grant W. Montgomery
    • , Jacob Gratten
    • , Jian Yang
    • , Peter M. Visscher
    • , Jian Yang
    •  & Jacob Gratten
  21. Institute for Social and Economic Research, University of Essex, Colchester, UK

    • Yanchun Bao
    • , Melissa C. Smart
    •  & Meena Kumari
  22. Seminar for Statistics, Department of Mathematics, ETH Zurich, Zurich, Switzerland

    • Laura Buzdugan
  23. Department of Economics, University of Zurich, Zurich, Switzerland

    • Laura Buzdugan
    •  & Ernst Fehr
  24. Stuyvesant High School, New York, NY, USA

    • Ann H. Caplin
  25. Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

    • Chia-Yen Chen
    •  & Aarno Palotie
  26. Nuffield Department of Population Health, University of Oxford, Oxford, UK

    • Peter Eibich
    •  & Peter Eibich
  27. Socio-Economic Panel Study, DIW Berlin, Berlin, Germany

    • Peter Eibich
    • , Peter Eibich
    • , Martin Kroh
    •  & Gert G. Wagner
  28. Max Planck Institute for Demographic Research, Rostock, Germany

    • Peter Eibich
    •  & Peter Eibich
  29. Research, 23andMe, Inc., Mountain View, CA, USA

    • Pierre Fontanillas
    • , Aaron Kleinman
    • , Michelle Agee
    • , Babak Alipanahi
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Nicholas A. Furlotte
    • , Karen E. Huber
    • , Nadia K. Litterman
    • , Jennifer C. McCreight
    • , Matthew H. McIntyre
    • , Joanna L. Mountain
    • , Carrie A. M. Northover
    • , Steven J. Pitts
    • , J. Fah Sathirapongsasuti
    • , Olga V. Sazonova
    • , Janie F. Shelton
    • , Suyash Shringarpure
    • , Chao Tian
    • , Joyce Y. Tung
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , Nicholas A. Furlotte
    • , David A. Hinds
    • , Joyce Y. Tung
    • , Adam Auton
    •  & David A. Hinds
  30. Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain

    • Juan R. Gonzalez
  31. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    • Juan R. Gonzalez
  32. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

    • Juan R. Gonzalez
  33. Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland

    • Peter K. Joshi
    • , Katharina E. Schraut
    • , Harry Campbell
    • , Peter K. Joshi
    • , Igor Rudan
    • , Ozren Polasek
    • , James F. Wilson
    • , David W. Clark
    • , Paul R. H. J. Timmers
    •  & James F. Wilson
  34. Center for Life Course Health Research, University of Oulu, Oulu, Finland

    • Ville Karhunen
    •  & Minna Männikkö
  35. Department of Economics, University of California San Diego, La Jolla, CA, USA

    • Remy Z. Levin
  36. Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany

    • Christina M. Lill
    • , Lars Bertram
    •  & Lars Bertram
  37. Team Loyalty BV, Hoofddorp, the Netherlands

    • Gerardus A. Meddens
    •  & Gerardus A. Meddens
  38. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

    • Gerard Muntané
    • , Carlos Morcillo-Suarez
    •  & Arcadi Navarro
  39. Research Department, Hospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain

    • Gerard Muntané
  40. Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Reus, Spain

    • Gerard Muntané
  41. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

    • Sandra Sanchez-Roige
    • , Abraham A. Palmer
    •  & Murray B. Stein
  42. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA

    • Jason D. Boardman
  43. Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA

    • Jason D. Boardman
  44. Department of Sociology, University of Colorado Boulder, Boulder, CO, USA

    • Jason D. Boardman
  45. Department of Economics and Finance, Oulu Business School, University of Oulu, Oulu, Finland

    • Andrew Conlin
    •  & Rauli Svento
  46. Department of Economics, University of Konstanz, Konstanz, Germany

    • Urs Fischbacher
  47. Thurgau Institute of Economics, Kreuzlingen, Switzerland

    • Urs Fischbacher
  48. Department of Econometrics, Erasmus University Rotterdam, Rotterdam, Rotterdam, the Netherlands

    • Patrick J. F. Groenen
    •  & Patrick J. F. Groenen
  49. Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Kathleen Mullan Harris
  50. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Kathleen Mullan Harris
  51. Unit of Psychiatry Research, University of Fribourg, Fribourg, Switzerland

    • Gregor Hasler
  52. Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA

    • Sonia Jain
    •  & Murray B. Stein
  53. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    • Patrick Sullivan
    • , Robert Karlsson
    • , Paul Lichtenstein
    • , Nancy L. Pedersen
    • , Patrik K. E. Magnusson
    • , Robert Karlsson
    •  & Patrik K. E. Magnusson
  54. Department of Health Care Policy, Harvard Medical School, Boston, MA, USA

    • Ronald C. Kessler
  55. SURFsara, Amsterdam, the Netherlands

    • Maarten Kooyman
  56. Peter Boris Centre for Addictions Research, McMaster University/St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada

    • James MacKillop
  57. Homewood Research Institute, Guelph, Ontario, Canada

    • James MacKillop
  58. Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA

    • Matthew B. McQueen
  59. Department of Economics, University of Munich, Munich, Germany

    • Klaus M. Schmidt
  60. Department of Economics, University of Cologne, Cologne, Germany

    • Matthias Sutter
  61. Experimental Economics Group, Max Planck Institute for Research into Collective Goods, Bonn, Germany

    • Matthias Sutter
  62. Department of Public Finance, University of Innsbruck, Innsbruck, Austria

    • Matthias Sutter
  63. Montpellier Business School, Montpellier, France

    • A. Roy Thurik
    •  & A. Roy Thurik
  64. Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands

    • Joyce van Meurs
    • , Joost Verlouw
    • , André G. Uitterlinden
    •  & André G. Uitterlinden
  65. UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK

    • Jon White
  66. Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA

    • Alan R. Sanders
    • , Pablo V. Gejman
    •  & Harriet de Wit
  67. Queensland Brain Institute, The University of Queensland, Brisbane, Australia

    • Jian Yang
    • , Guo-Bo Chen
    • , Zhihong Zhu
    • , Andrew Bakshi
    • , Riccardo E. Marioni
    • , Anna A. E. Vinkhuyzen
    • , Jian Yang
    •  & Jian Yang
  68. Dept of Psychology, University of Olso, Oslo, Norway

    • Lars Bertram
    •  & Lars Bertram
  69. School of Public Health, Imperial College London, London, UK

    • Lars Bertram
    •  & Lars Bertram
  70. Estonian Genome Center, University of Tartu, Tartu, Estonia

    • Tõnu Esko
    • , Anette Kalnapenkis
    • , Silva Kasela
    • , Jaanika Kronberg-Guzman
    • , Viktorija Kukushkina
    • , Andres Metspalu
    • , Lili Milani
    • , Natalia Pervjakova
    • , Evelin Mihailov
    • , Natalia Pervjakova
    • , Reedik Mägi
    • , Lili Milani
    • , Andres Metspalu
    • , Tõnu Esko
    •  & Tõnu Esko
  71. Department of Economics, Stockholm School of Economics, Stockholm, Sweden

    • Magnus Johannesson
    •  & Magnus Johannesson
  72. Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA

    • Michelle N. Meyer
    •  & Michelle N. Meyer
  73. Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain

    • Arcadi Navarro
  74. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain

    • Arcadi Navarro
  75. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA

    • Abraham A. Palmer
  76. Department of Clinical Genetics, VU Medical Centre, Amsterdam, the Netherlands

    • Danielle Posthuma
    •  & Danielle Posthuma
  77. Department of Economics, Johannes Gutenberg University, Mainz, Germany

    • Daniel Schunk
  78. Behavioral and Health Genomics Center, Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA

    • Patrick Turley
    • , Daniel J. Benjamin
    • , Patrick Turley
    •  & Daniel J. Benjamin
  79. Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    • Robert J. Ursano
  80. Max Planck Institute for Human Development, Berlin, Germany

    • Tian Liu
    •  & Gert G. Wagner
  81. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland

    • Jennifer E. Huffman
    • , Jonathan Marten
    • , Caroline Hayward
    • , Veronique Vitart
    • , James F. Wilson
    • , Alan F. Wright
    •  & James F. Wilson
  82. Mater Medical Research Institute, Translational Research Institute, Brisbane, Australia

    • Jacob Gratten
    •  & Jacob Gratten
  83. Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA

    • James J. Lee
    • , Michael B. Miller
    • , William G. Iacono
    • , Matt McGue
    • , Robert F. Krueger
    •  & James J. Lee
  84. Department of Economics, New York University, New York, NY, USA

    • Kevin Thom
    • , David Cesarini
    •  & David Cesarini
  85. Department of Economics, University of Southern California, Los Angeles, CA, USA

    • Daniel J. Benjamin
    •  & Daniel J. Benjamin
  86. National Bureau of Economic Research, Cambridge, MA, USA

    • Daniel J. Benjamin
    •  & Daniel J. Benjamin
  87. German Institute for Economic Research, DIW Berlin, Berlin, Germany

    • Philipp D. Koellinger
    •  & Philipp D. Koellinger
  88. Computational Biology, Ontario Institute for Cancer Research, Toronto, Canada

    • Mawussé Agbessi
    • , Isabel Alves
    • , Philip Awadalla
    •  & Marie-Julie Favé
  89. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA

    • Habibul Ahsan
    • , Brandon Pierce
    •  & Lin Tong
  90. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

    • Anand Andiappan
    • , Bernett Lee
    •  & Olaf Rotzchke
  91. Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA

    • Alexis Battle
    • , Yungil Kim
    •  & Ashis Saha
  92. Heart Center Leipzig, Universität Leipzig, Leipzig, Germany

    • Frank Beutner
  93. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    • Marc Jan Bonder
    • , Annique Claringbould
    • , Patrick Deelen
    • , Lude Franke
    • , Urmo Võsa
    • , Harm-Jan Westra
    • , Harm-Jan Westra
    • , Lude Franke
    •  & Pim van der Harst
  94. Cardiovascular Health Research Unit, Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, WA, USA

    • Mark Christiansen
    •  & Bruce M. Psaty
  95. Medical School, University of Exeter, Exeter, UK

    • Timothy Frayling
    •  & Hanieh Yaghootkar
  96. Department of Medicine, University of Washington, Seattle, WA, USA

    • Sina A. Gharib
  97. Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

    • Sina A. Gharib
  98. School of Biological Sciences, Georgia Tech, Atlanta, GA, USA

    • Gregory Gibson
    • , Urko M. Marigorta
    •  & Biao Zeng
  99. Leiden University Medical Centre, Leiden, the Netherlands

    • Bastiaan Heijmans
  100. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    • Gibran Hemani
    • , Susan Ring
    • , Beate St Pourcain
    • , David M. Evans
    • , George McMahon
    • , Lavinia Paternoster
    • , Susan M. Ring
    • , Thorkild I. A. Sørensen
    • , Nicholas J. Timpson
    •  & George Davey Smith
  101. Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    • Rick Jansen
    • , Michel G. Nivard
    • , Brenda Penninx
    • , Jenny van Dongen
    •  & Brenda Penninx
  102. Department of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Mika Kähönen
    •  & Mika Kähönen
  103. University of Helsinki, Helsinki, Finland

    • Johannes Kettunen
    •  & Samuli Ripatti
  104. Genetics and Genomic Science Department, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Yungil Kim
  105. Institut für Medizinische Informatik, Statistik und Epidemiologie, Leipzig Research Centre for Civilization Diseases (LIFE), Universität Leipzig, Leipzig, Germany

    • Holger Kirsten
    • , Markus Loeffler
    •  & Markus Scholz
  106. IFB Adiposity Diseases, Universität Leipzig, Leipzig, Germany

    • Peter Kovacs
  107. Interdisciplinary Center for Clinical Research, Faculty of Medicine, Universität Leipzig, Leipzig, Germany

    • Knut Krohn
  108. Lausanne University Hospital, Lausanne, Switzerland

    • Zoltan Kutalik
    • , Sina Rüeger
    •  & Zoltan Kutalik
  109. Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Terho Lehtimäki
    • , Ilkka Seppälä
    •  & Terho Lehtimäki
  110. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    • Martina Müller-Nurasyid
    • , Katharina Schramm
    •  & Konstantin Strauch
  111. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

    • Matthias Nauck
  112. National Institute for Health and Welfare, University of Helsinki, Helsinki, Finland

    • Markus Perola
    • , Niina Eklund
    • , Seppo Koskinen
    • , Tomi Mäki-Opas
    • , Veikko Salomaa
    • , Jaakko Kaprio
    •  & Markus Perola
  113. Garvan Institute of Medical Research, Garvan-Weizmann Centre for Cellular Genomics, Sydney, New South Wales, Australia

    • Joseph Powell
  114. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    • Holger Prokisch
    • , Peter Lichtner
    •  & Thomas Meitinger
  115. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital and University of Turku, Turku, Finland

    • Olli Raitakari
    •  & Olli Raitakari
  116. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK

    • Susan Ring
  117. Department of Medicine, Universität Leipzig, Leipzig, Germany

    • Michael Stumvoll
    •  & Anke Tönjes
  118. Radboud University Medical Center, Radboud University, Nijmegen, the Netherlands

    • Peter-Bram t Hoen
    • , Tessel E. Galesloot
    •  & Lambertus A. L. M. Kiemeney
  119. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    • Alexander Teumer
    • , Alexander Teumer
    • , Sebastian E. Baumeister
    • , Henry Völzke
    •  & Wolfgang Hoffmann
  120. Institute for Laboratory Medicine, Leipzig Research Center for Civilization Diseases (LIFE), Universität Leipzig, Leipzig, Germany

    • Joachim Thiery
  121. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany

    • Uwe Völker
    • , Georg Homuth
    •  & Uwe Völker
  122. Icelandic Heart Association, Kopavogur, Iceland

    • Valur Emilsson
    • , Albert V. Smith
    •  & Vilmundur Gudnason
  123. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, Iceland

    • Valur Emilsson
  124. Department of Government, Uppsala University, Uppsala, Sweden

    • Sven Oskarsson
    •  & Karl-Oskar Lindgren
  125. New York Genome Center, New York, NY, USA

    • Joseph K. Pickrell
  126. Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

    • Tarunveer S. Ahluwalia
    • , Klaus Bønnelykke
    • , Johannes Waage
    •  & Hans Bisgaard
  127. Steno Diabetes Center, Gentofte, Denmark

    • Tarunveer S. Ahluwalia
    •  & Johannes Waage
  128. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden

    • Jonas Bacelis
    •  & Bo Jacobsson
  129. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    • Clemens Baumbach
    •  & Christian Gieger
  130. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    • Clemens Baumbach
    •  & Christa Meisinger
  131. deCODE Genetics/Amgen Inc., Reykjavik, Iceland

    • Gyda Bjornsdottir
    • , Augustine Kong
    • , Gudmar Thorleifsson
    • , Bjarni V. Halldórsson
    • , Kari Stefansson
    •  & Unnur Thorsteinsdottir
  132. Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands

    • Johannes H. Brandsma
    •  & Raymond A. Poot
  133. Istituto di Ricerca Genetica e Biomedica UOS di Sassari, National Research Council of Italy, Sassari, Italy

    • Maria Pina Concas
    • , Bjarni Gunnarsson
    • , Simona Vaccargiu
    •  & Mario Pirastu
  134. Psychology, University of Illinois, Champaign, IL, USA

    • Jaime Derringer
  135. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

    • Giorgia Girotto
    • , Dragana Vuckovic
    • , Ilaria Gandin
    • , Paolo Gasparini
    •  & Nicola Pirastu
  136. Department of Public Health, University of Helsinki, Helsinki, Finland

    • Richa Gupta
    • , Antti Latvala
    • , Anu Loukola
    •  & Jaakko Kaprio
  137. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

    • Leanne M. Hall
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  138. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK

    • Leanne M. Hall
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  139. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

    • Sarah E. Harris
    • , Gail Davies
    • , David C. M. Liewald
    • , Riccardo E. Marioni
    •  & Ian J. Deary
  140. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Sarah E. Harris
    •  & David J. Porteous
  141. Department of Neurology, General Hospital and Medical University Graz, Graz, Austria

    • Edith Hofer
    • , Katja E. Petrovic
    • , Helena Schmidt
    •  & Reinhold Schmidt
  142. Institute for Medical Informatics, Statistics and Documentation, General Hospital and Medical University Graz, Graz, Austria

    • Edith Hofer
  143. Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK

    • Momoko Horikoshi
  144. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    • Momoko Horikoshi
  145. Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland

    • Kadri Kaasik
    • , Jari Lahti
    • , Liisa Keltigangas-Järvinen
    •  & Katri Räikkönen
  146. Nutrition and Dietetics, Health Science and Education, Harokopio University, Athens, Greece

    • Ioanna P. Kalafati
    •  & George V. Dedoussis
  147. Folkhälsan Research Centre, Helsingfors, Finland

    • Jari Lahti
    • , Katri Räikkönen
    •  & Johan G. Eriksson
  148. Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands

    • Christiaan de Leeuw
  149. Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Penelope A. Lind
    •  & Sarah E. Medland
  150. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK

    • Massimo Mangino
    • , Lydia Quaye
    • , Cristina Venturini
    •  & Tim D. Spector
  151. NIHR Biomedical Research Centre, Guy’s and St. Thomas’ Foundation Trust, London, UK

    • Massimo Mangino
    •  & Cristina Venturini
  152. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    • Peter J. van der Most
    • , Behrooz Z. Alizadeh
    •  & Judith M. Vonk
  153. Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    • Christopher Oldmeadow
    • , Elizabeth G. Holliday
    •  & John R. Attia
  154. Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

    • Christopher Oldmeadow
    • , Elizabeth G. Holliday
    • , Rodney J. Scott
    •  & John R. Attia
  155. Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, UK

    • Antony Payton
    •  & William E. R. Ollier
  156. Human Communication and Deafness, School of Psychological Sciences, University of Manchester, Manchester, UK

    • Antony Payton
  157. Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands

    • Wouter J. Peyrot
    •  & Yusplitri Milaneschi
  158. GGZ inGeest, Amsterdam, the Netherlands

    • Wouter J. Peyrot
    •  & Yusplitri Milaneschi
  159. Laboratory of Genetics, National Institute on Aging, Baltimore, MD, USA

    • Yong Qian
    • , Jun Ding
    •  & David Schlessinger
  160. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland

    • Rico Rueedi
  161. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    • Rico Rueedi
  162. Department Of Health Sciences, University of Milan, Milano, Italy

    • Erika Salvi
    •  & Daniele Cusi
  163. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany

    • Börge Schmidt
    • , Lewin Eisele
    •  & Karl-Heinz Jöckel
  164. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    • Jianxin Shi
  165. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    • Albert V. Smith
    • , Vilmundur Gudnason
    • , Kari Stefansson
    •  & Unnur Thorsteinsdottir
  166. School of Oral and Dental Sciences, University of Bristol, Bristol, UK

    • Beate St Pourcain
  167. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    • Niek Verweij
    • , Klaus Berger
    •  & Pim van der Harst
  168. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

    • Juergen Wellmann
  169. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA

    • Jingyun Yang
    • , Patricia A. Boyle
    •  & David A. Bennett
  170. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

    • Jingyun Yang
    •  & David A. Bennett
  171. Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA

    • Wei Zhao
    • , Jennifer A. Smith
    • , Erin B. Ware
    •  & Sharon L. R. Kardia
  172. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    • Behrooz Z. Alizadeh
  173. Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany

    • Sebastian E. Baumeister
  174. Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy

    • Ginevra Biino
  175. Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA

    • Patricia A. Boyle
  176. Warwick Medical School, University of Warwick, Coventry, UK

    • Francesco P. Cappuccio
  177. Department of Psychology, University of Edinburgh, Edinburgh, UK

    • Gail Davies
    • , David C. M. Liewald
    •  & Ian J. Deary
  178. Saïd Business School, University of Oxford, Oxford, UK

    • Jan-Emmanuel De Neve
  179. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    • Panos Deloukas
    •  & Stavroula Kanoni
  180. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia

    • Panos Deloukas
  181. The Berlin Aging Study II Research Group on Geriatrics, Charité–Universitätsmedizin Berlin, Berlin, Germany

    • Ilja Demuth
    •  & Elisabeth Steinhagen-Thiessen
  182. Institute of Medical and Human Genetics, Charité–Universitätsmedizin Berlin, Berlin, Germany

    • Ilja Demuth
  183. University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia

    • David M. Evans
  184. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

    • Jessica D. Faul
    •  & David R. Weir
  185. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    • Mary F. Feitosa
    • , Aldi T. Kraja
    • , Ingrid B Borecki
    •  & Michael A. Province
  186. Institute of Human Genetics, University of Bonn, Bonn, Germany

    • Andreas J. Forstner
  187. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    • Andreas J. Forstner
  188. Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik, Iceland

    • Bjarni V. Halldórsson
  189. Laboratory of Epidemiology & Population Science, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    • Tamara B. Harris
  190. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA

    • Andrew C. Heath
    •  & Pamela A. Madden
  191. Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK

    • Lynne J. Hocking
  192. Manchester Medical School, University of Manchester, Manchester, UK

    • Michael A. Horan
  193. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Philip L. de Jager
    •  & Aarno Palotie
  194. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA

    • Philip L. de Jager
  195. Harvard Medical School, Boston, Massachusetts, USA

    • Philip L. de Jager
  196. Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway

    • Astanand Jugessur
    • , Ronny Myhre
    •  & Bo Jacobsson
  197. Department of Genomics of Common Disease, Imperial College London, London, UK

    • Marika A. Kaakinen
  198. Public Health, Medical School, University of Split, Split, Croatia

    • Ivana Kolcic
  199. Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    • Lenore J. Launer
  200. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

    • Douglas F. Levinson
  201. Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Riccardo E. Marioni
  202. Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    • Pedro Marques-Vidal
    •  & Peter Vollenweider
  203. Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Dale R. Nyholt
  204. Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, Queensland, Australia

    • Dale R. Nyholt
  205. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    • Aarno Palotie
  206. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    • Aarno Palotie
    • , Antti-Pekka Sarin
    •  & Jaakko Kaprio
  207. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    • Aarno Palotie
  208. Medical Genetics, Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo’, Trieste, Italy

    • Antonietta Robino
    • , Sheila Ulivi
    •  & Paolo Gasparini
  209. Social Impact, Arlington, VA, USA

    • Olga Rostapshova
    •  & Diego Vozzi
  210. Department of Economics, University of Minnesota Twin Cities, Minneapolis, MN, USA

    • Aldo Rustichini
  211. Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA

    • Alan R. Sanders
    •  & Pablo V. Gejman
  212. Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

    • Antti-Pekka Sarin
  213. Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, Austria

    • Helena Schmidt
  214. Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    • Rodney J. Scott
  215. Medical Research Institute, University of Dundee, Dundee, UK

    • Blair H. Smith
  216. Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science, University of Leuven, Leuven, Belgium

    • Jan A. Staessen
  217. R&D VitaK Group, Maastricht University, Maastricht, the Netherlands

    • Jan A. Staessen
  218. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universität, Munich, Germany

    • Konstantin Strauch
  219. Department of Geriatrics, Florida State University College of Medicine, Tallahassee, FL, USA

    • Antonio Terracciano
  220. Department of Health Sciences and Genetics, University of Leicester, Leicester, UK

    • Martin D. Tobin
  221. Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

    • Erin B. Ware
  222. Department of Health Sciences, Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    • Ute Bültmann
  223. Department of Psychology, Union College, Schenectady, NY, USA

    • Christopher F. Chabris
  224. Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, Cagliari, Italy

    • Francesco Cucca
  225. Institute of Biomedical Technologies, Italian National Research Council, Milan, Italy

    • Daniele Cusi
  226. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland

    • Johan G. Eriksson
  227. Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, the Netherlands

    • Barbara Franke
  228. Experimental Genetics Division, Sidra, Doha, Qatar

    • Paolo Gasparini
  229. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

    • Hans-Jörgen Grabe
  230. Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund, Germany

    • Hans-Jörgen Grabe
  231. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands

    • Pim van der Harst
  232. Generation Scotland, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Caroline Hayward
  233. Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia

    • Elina Hyppönen
  234. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    • Elina Hyppönen
  235. Population, Policy and Practice, UCL Institute of Child Health, London, UK

    • Elina Hyppönen
    •  & Christine Power
  236. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    • Marjo-Riitta Järvelin
  237. Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland

    • Marjo-Riitta Järvelin
  238. Unit of Primary Care, Oulu University Hospital, Oulu, Finland

    • Marjo-Riitta Järvelin
  239. Biocenter Oulu, University of Oulu, Oulu, Finland

    • Marjo-Riitta Järvelin
  240. Economics, NYU Shanghai, Pudong, China

    • Steven F. Lehrer
  241. Policy Studies, Queen’s University, Kingston, Ontario, Canada

    • Steven F. Lehrer
  242. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Nicholas G. Martin
  243. Centre for Clinical and Cognitive Neuroscience, Institute of Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester, UK

    • Neil Pendleton
  244. Manchester Institute for Collaborative Research in Ageing, University of Manchester, Manchester, UK

    • Neil Pendleton
  245. Faculty of Medicine, University of Split, Split, Croatia

    • Ozren Polasek
  246. Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark

    • Thorkild I. A. Sørensen
  247. Department of Sociology, New York University, New York, NY, USA

    • Dalton C. Conley
  248. School of Medicine, New York University, New York, NY, USA

    • Dalton C. Conley

Authors

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Consortia

  1. 23and Me Research Team

  1. eQTLgen Consortium

  1. International Cannabis Consortium

    1. Social Science Genetic Association Consortium

    Contributions

    J.P.B., P.D.K., and D.J.B. designed and oversaw the study. J.P.B. closely supervised the analyses and led the writing of the manuscript. R.K.L. was the lead analyst, responsible for quality control, the meta-analyses, summarizing the overlap across the results of the various GWAS, and the SNP heritability analyses. E.K. conducted the population stratification, replication, and proxy-phenotype analyses. R.W. led the genetic correlation analyses, and M.A.F. contributed to those analyses. P.B. led the polygenic score prediction analyses, and R.K.L., E.K., R.W., A.A., R.d.V., M.A.F., and M.G.N. contributed to those analyses. P.B. and C.L.Z. conducted the MTAG analyses. The bioinformatics analyses were led by S.F.W.M. Analysts who assisted S.F.W.M. include J.G. and M.T. (SMR), A.R.H. (MAGMA), G.A.M. (Gene Network), and P.N.T. (DEPICT). M.L. conducted the review of the literature attempting to link risk tolerance to biological pathways. R.K.L. prepared the majority of figures; E.K. and S.P.T. also prepared some figures. A.O., C.A.R., and S.P.T. helped with several additional analyses. D.C., J.G., and J.J.L. provided helpful advice and feedback on various aspects of the study design. All authors contributed to and critically reviewed the manuscript. P.B., R.K.L., E.K., S.F.W.M., and R.W. made especially major contributions to the writing and editing; these authors contributed equally, and lead authors 2–5 are listed aphabetically in the author list.

    Competing interests

    A. Auton, P.F., D.A.H., and A.K. are employees of 23andMe. R.C.K., in the past three years, received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Sage Pharmaceuticals, Shire, and Takeda; and served on an advisory board for the Johnson & Johnson Services Inc. Lake Nona Life Project. R.C.K. is a co-owner of DataStat Inc., a market research firm that carries out healthcare research. J.M. is a principal in BEAM Diagnostics Inc. The authors declare no other competing interests.

    Corresponding authors

    Correspondence to Richard Karlsson Linnér or Jonathan P. Beauchamp.

    Supplementary information

    1. Supplementary Text and Figures

      Supplementary Figures 1–16 and Supplementary Note

    2. Reporting Summary

    3. Supplementary Tables

      Supplementary Tables 1–10

    4. Supplementary Data

      LocusZoom plots

    About this article

    Publication history

    Received

    Accepted

    Published

    DOI

    https://doi.org/10.1038/s41588-018-0309-3