Article

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

  • Nature Genetics volume 48, pages 624633 (2016)
  • doi:10.1038/ng.3552
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Abstract

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

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Change history

  • Corrected online 27 June 2016

    In the version of this article initially published, the following co-authors and their affiliations were incorrectly omitted from the author list: Gudmar Thorleifsson, Sven Bergmann, Gyda Bjornsdottir, David C. Liewald, John M. Starr, Kari Stefansson and Unnur Thorsteinsdottir. In addition, the middle initial for co-author Andreas J. Forstner was also omitted. The errors have been corrected in the HTML and PDF versions of the article.

  • Corrected online 29 August 2016

    In the version of this article initially published, one of the affiliations listed for author Maciej Trzaskowski, to the Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia, was included in error. The correct affiliation for this author is the Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We are grateful to P.M. Visscher for advice, support, and feedback. We thank S. Cunningham and N. Galla for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The SSGAC seeks to facilitate studies that investigate the influence of genes on human behavior, well-being, and social–scientific outcomes using large GWAS meta-analyses. The SSGAC also provides opportunities for replication and promotes the collection of accurately measured, harmonized phenotypes across cohorts. The SSGAC operates as a working group within the CHARGE Consortium. This research has also been conducted using the UK Biobank Resource. The study was supported by funding from the US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium'), a supplementary grant from the National Institute of Health Office of Behavioral and Social Science Research, the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER and R01-AG042568-02 to the University of Southern California. A full list of acknowledgments is provided in the Supplementary Note.

Author information

Author notes

    • Aysu Okbay
    • , Bart M L Baselmans
    • , Jan-Emmanuel De Neve
    • , Patrick Turley
    • , Michel G Nivard
    • , Mark Alan Fontana
    • , S Fleur W Meddens
    • , Richard Karlsson Linnér
    •  & Cornelius A Rietveld

    These authors contributed equally to this work.

    • Robert F Krueger
    • , Jonathan P Beauchamp
    • , Philipp D Koellinger
    • , Daniel J Benjamin
    • , Meike Bartels
    •  & David Cesarini

    These authors jointly directed this work.

Affiliations

  1. Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.

    • Aysu Okbay
    • , Cornelius A Rietveld
    • , Ronald de Vlaming
    •  & A Roy Thurik
  2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Aysu Okbay
    • , Cornelius A Rietveld
    • , Ronald de Vlaming
    • , Sven J van der Lee
    • , Sara M Willems
    • , Najaf Amin
    • , Nese Direk
    • , Cornelia M van Duijn
    • , Henning Tiemeier
    • , André G Uitterlinden
    •  & Albert Hofman
  3. Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.

    • Aysu Okbay
    • , S Fleur W Meddens
    • , Richard Karlsson Linnér
    • , Cornelius A Rietveld
    • , Ronald de Vlaming
    • , Patrick J F Groenen
    • , A Roy Thurik
    • , André G Uitterlinden
    •  & Philipp D Koellinger
  4. Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.

    • Bart M L Baselmans
    • , Michel G Nivard
    • , Camelia C Minica
    • , Jouke-Jan Hottenga
    • , Dorret I Boomsma
    • , Eco J C de Geus
    •  & Meike Bartels
  5. EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.

    • Bart M L Baselmans
    • , Jouke-Jan Hottenga
    • , Dorret I Boomsma
    • , Eco J C de Geus
    •  & Meike Bartels
  6. Saïd Business School, University of Oxford, Oxford, UK.

    • Jan-Emmanuel De Neve
  7. Department of Economics, Harvard University, Cambridge, Massachusetts, USA.

    • Patrick Turley
    • , David I Laibson
    •  & Jonathan P Beauchamp
  8. Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.

    • Mark Alan Fontana
    •  & Daniel J Benjamin
  9. Department of Complex Trait Genetics, Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands.

    • S Fleur W Meddens
    • , Richard Karlsson Linnér
    •  & Philipp D Koellinger
  10. Amsterdam Business School, University of Amsterdam, Amsterdam, the Netherlands.

    • S Fleur W Meddens
    • , Richard Karlsson Linnér
    •  & Philipp D Koellinger
  11. Department of Psychology, University of Illinois, Champaign, Illinois, USA.

    • Jaime Derringer
  12. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.

    • Jacob Gratten
    • , Andrew Bakshi
    • , Maciej Trzaskowski
    • , Anna E Vinkhuyzen
    •  & Jian Yang
  13. Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.

    • James J Lee
    • , Lindsay Matteson
    • , Michael B Miller
    • , William G Iacono
    • , Matt McGue
    •  & Robert F Krueger
  14. New York Genome Center, New York, New York, USA.

    • Jimmy Z Liu
    •  & Joseph K Pickrell
  15. COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

    • Tarunveer S Ahluwalia
  16. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.

    • Tarunveer S Ahluwalia
    • , Torben Hansen
    •  & Thorkild I A Sørensen
  17. Steno Diabetes Center, Gentofte, Denmark.

    • Tarunveer S Ahluwalia
  18. Department of Public Health, University of Helsinki, Helsinki, Finland.

    • Jadwiga Buchwald
    • , Juho Wedenoja
    • , Richa Gupta
    • , Anu Loukola
    •  & Jaakko Kaprio
  19. Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.

    • Alana Cavadino
  20. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

    • Alana Cavadino
    • , Elina Hyppönen
    •  & Christine Power
  21. USDA–ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.

    • Alexis C Frazier-Wood
  22. 23andMe, Inc., Mountain View, California, USA.

    • Nicholas A Furlotte
    •  & David A Hinds
  23. Department of Epidemiology and Public Health, University College London, London, UK.

    • Victoria Garfield
    •  & Andrew Steptoe
  24. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany.

    • Marie Henrike Geisel
    • , Börge Schmidt
    •  & Karl-Heinz Jöckel
  25. Centre for Research in Environmental Epidemiology, Institute for Global Health, Barcelona, Spain.

    • Juan R Gonzalez
  26. Universitat Pompeu Fabra, Barcelona, Spain.

    • Juan R Gonzalez
  27. CIBER Epidemiología y Salud Pública, Barcelona, Spain.

    • Juan R Gonzalez
  28. Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.

    • Saskia Haitjema
    • , Sander W van der Laan
    • , Gerard Pasterkamp
    •  & Hester M den Ruijter
  29. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Robert Karlsson
    • , Patrik K E Magnusson
    •  & Nancy L Pedersen
  30. Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Karl-Heinz Ladwig
    •  & Rebecca T Emeny
  31. Department of Psychosomatic Medicine and Psychotherapy, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.

    • Karl-Heinz Ladwig
  32. Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.

    • Jari Lahti
    • , Laura Pulkki-Råback
    • , Katri Räikkönen
    •  & Liisa Keltikangas-Järvinen
  33. Folkhälsan Research Centre, Helsingfors, Finland.

    • Jari Lahti
  34. Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.

    • Jari Lahti
    •  & Laura Pulkki-Råback
  35. Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Penelope A Lind
    •  & Sarah E Medland
  36. Max Planck Institute for Human Development, Berlin, Germany.

    • Tian Liu
    •  & Gert G Wagner
  37. Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany.

    • Tian Liu
  38. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Evelin Mihailov
    • , Andres Metspalu
    •  & Tõnu Esko
  39. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Ilja M Nolte
    • , Peter J van der Most
    • , Harold Snieder
    •  & Behrooz Z Alizadeh
  40. Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

    • Dennis Mook-Kanamori
    • , Ruifang Li-Gao
    • , Renée de Mutsert
    •  & Frits R Rosendaal
  41. Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.

    • Dennis Mook-Kanamori
  42. BESC, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

    • Dennis Mook-Kanamori
  43. Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.

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

    • Christopher Oldmeadow
    • , Elizabeth G Holliday
    • , Rodney J Scott
    •  & John R Attia
  45. Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.

    • Yong Qian
    • , Jun Ding
    •  & David Schlessinger
  46. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

    • Olli Raitakari
  47. Department of Clinical Physiology, Turku University Hospital, Turku, Finland.

    • Olli Raitakari
  48. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Rajesh Rawal
    •  & Christian Gieger
  49. Department of Psychology, University of Tartu, Tartu, Estonia.

    • Anu Realo
  50. Department of Psychology, University of Warwick, Coventry, UK.

    • Anu Realo
  51. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.

    • Rico Rueedi
    •  & Sven Bergmann
  52. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Rico Rueedi
    •  & Sven Bergmann
  53. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  54. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    • , Vilmundur Gudnason
    • , Kari Stefansson
    •  & Unnur Thorsteinsdottir
  55. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

    • Evie Stergiakouli
    • , Oliver S P Davis
    • , Lavinia Paternoster
    • , Claire M A Haworth
    • , Thorkild I A Sørensen
    • , Nicholas J Timpson
    •  & George Davey Smith
  56. National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    • , Luigi Ferrucci
    • , Angelina R Sutin
    •  & Antonio Terracciano
  57. Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA, Torrence, California, USA.

    • Kent Taylor
  58. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.

    • Gudmar Thorleifsson
    • , Gyda Bjornsdottir
    • , Kari Stefansson
    •  & Unnur Thorsteinsdottir
  59. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.

    • Juergen Wellmann
    •  & Klaus Berger
  60. Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Harm-Jan Westra
  61. Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Harm-Jan Westra
  62. Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.

    • Wei Zhao
    • , Jennifer A Smith
    •  & Sharon L R Kardia
  63. Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.

    • Patricia A Boyle
  64. RAND Corporation, Santa Monica, California, USA.

    • Samantha Cherney
  65. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

    • Simon R Cox
    • , Gail Davies
    • , David C Liewald
    • , Ian J Deary
    •  & John M Starr
  66. Department of Psychology, University of Edinburgh, Edinburgh, UK.

    • Simon R Cox
    • , Gail Davies
    • , Alison Pattie
    •  & Ian J Deary
  67. German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany.

    • Peter Eibich
    •  & Gert G Wagner
  68. Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

    • Peter Eibich
  69. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.

    • Rebecca T Emeny
  70. Farr Institute of Health Informatics, University College London, London, UK.

    • Ghazaleh Fatemifar
  71. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.

    • Jessica D Faul
    •  & David R Weir
  72. Institute of Human Genetics, University of Bonn, Bonn, Germany.

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

    • Andreas J Forstner
  74. Laboratory of Epidemiology, Demography, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.

    • Tamara B Harris
  75. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Juliette M Harris
    • , Lydia Quaye
    •  & Tim D Spector
  76. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Philip L De Jager
  77. Harvard Medical School, Boston, Massachusetts, USA.

    • Philip L De Jager
  78. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Philip L De Jager
  79. Department of Genomics of Common Disease, Imperial College London, London, UK.

    • Marika A Kaakinen
    •  & Marjo-Riitta Järvelin
  80. Center for Life Course Health Research, University of Oulu and Oulu University Hospital, Oulu, Finland.

    • Marika A Kaakinen
    •  & Ville Karhunen
  81. Department of Pediatrics, University of Helsinki, Helsinki, Finland.

    • Eero Kajantie
  82. National Institute for Health and Welfare, Helsinki, Finland.

    • Eero Kajantie
  83. Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.

    • Ivana Kolcic
    • , Delilah Zabaneh
    •  & Ozren Polasek
  84. Institute for Social and Economic Research, University of Essex, Wivenhoe Park, UK.

    • Meena Kumari
  85. Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.

    • Lenore J Launer
  86. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

    • Lude Franke
  87. Department of Neurology, General Hospital and Medical University Graz, Graz, Austria.

    • Marisa Koini
    • , Katja E Petrovic
    • , Helena Schmidt
    •  & Reinhold Schmidt
  88. Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

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

    • Grant W Montgomery
  90. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

    • Miriam A Mosing
  91. Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

    • Igor Rudan
  92. Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.

    • Rodney J Scott
  93. Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, Florida, USA.

    • Angelina R Sutin
    •  & Antonio Terracciano
  94. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.

    • Lei Yu
    •  & David A Bennett
  95. Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institute of Neurogenetics and Institute of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.

    • Lars Bertram
  96. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.

    • Lars Bertram
  97. Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.

    • Dorret I Boomsma
    • , Eco J C de Geus
    •  & Meike Bartels
  98. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Shun-Chiao Chang
  99. Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitarià di Monserrato, Monserrato, Italy.

    • Francesco Cucca
  100. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.

    • Johan G Eriksson
  101. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Johan G Eriksson
  102. Unit of General Practice, University Central Hospital, Helsinki, Finland.

    • Johan G Eriksson
  103. Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Ute Bültmann
  104. Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.

    • Patrick J F Groenen
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  105. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Catharine A Hartman
  106. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • Caroline Hayward
  107. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Andrew C Heath
  108. Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia.

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

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

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

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

    • Marjo-Riitta Järvelin
  113. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Jaakko Kaprio
  114. Department for Health, THL (National Institute for Health and Welfare), Helsinki, Finland.

    • Jaakko Kaprio
  115. Department of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
  116. Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Laura D Kubzansky
  117. Fimlab Laboratories, Tampere, Finland.

    • Terho Lehtimäki
  118. Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland.

    • Terho Lehtimäki
  119. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Nicholas G Martin
  120. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Andres Metspalu
  121. Department of Sociology, University of Oxford, Oxford, UK.

    • Melinda Mills
  122. Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.

    • Gerard Pasterkamp
  123. Social, Genetic and Developmental Psychiatry Centre, King's College London, De Crespigny Park, UK.

    • Robert Plomin
  124. Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.

    • Stephen S Rich
  125. Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University Graz, Graz, Austria.

    • Helena Schmidt
  126. Department of Economics, Oulu Business School, Oulu, Finland.

    • Rauli Svento
  127. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Behrooz Z Alizadeh
  128. Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, Capital Region, Frederiksberg, Denmark.

    • Thorkild I A Sørensen
  129. Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.

    • John M Starr
  130. Montpellier Business School, Montpellier, France.

    • A Roy Thurik
  131. Panteia, Zoetermeer, the Netherlands.

    • A Roy Thurik
  132. Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Henning Tiemeier
  133. Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Henning Tiemeier
  134. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.

    • André G Uitterlinden
  135. School of Economics and Management, Berlin University of Technology, Berlin, Germany.

    • Gert G Wagner
  136. University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.

    • Jian Yang
  137. Department of Sociology, Princeton University, Princeton, New Jersey, USA.

    • Dalton C Conley
  138. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Albert Hofman
  139. Department of Economics, Stockholm School of Economics, Stockholm, Sweden.

    • Magnus Johannesson
  140. Department of Bioethics, Clarkson University, Schenectady, New York, USA.

    • Michelle N Meyer
  141. Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Michelle N Meyer
  142. Department of Biological Sciences, Columbia University, New York, New York, USA.

    • Joseph K Pickrell
  143. Department of Economics, New York University, New York, New York, USA.

    • David Cesarini
  144. Research Institute for Industrial Economics, Stockholm, Sweden.

    • David Cesarini

Consortia

  1. LifeLines Cohort Study

    University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

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Contributions

M.B., D.J.B., D.C., J.-E.D.N., P.D.K., and R.F.K. designed and oversaw the study. A.O. and B.M.L.B. were responsible for quality control and meta-analyses. Bioinformatics analyses were carried out by J.P.B., T.E., M.A.F., J.R.G., J.J.L. S.F.W.M., M.G.N., and H.-J.W. Other follow-up analyses were conducted by M.A.F., J.P.B., P.T., A.O., B.M.L.B., and R.K.L. Especially major contributions to writing and editing were made by M.B., D.J.B., J.P.B., D.C.C., J.-E.D.N., P.D.K., A.J.O., and P.T. All authors contributed to and critically reviewed the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Philipp D Koellinger or Daniel J Benjamin or Meike Bartels.

Integrated supplementary information

Supplementary figures

  1. 1.

    Illustrating the tradeoff between maximizing sample size and having more precise and uniform phenotype measures across cohorts.

  2. 2.

    Local Manhattan plots of the association between SNPs on chromosome 8 and neuroticism in UKB.

  3. 3.

    Proxy-phenotype analyses: test of SNPs associated with subjective well-being at P < 1 × 10–4 for association with depressive symptoms and neuroticism.

  4. 4.

    Quantile–quantile plots for primary subjective well-being analysis, post hoc subjective well-being analysis using 1000 Genomes Project SNPs, life satisfaction analysis, and positive affect analysis.

  5. 5.

    Manhattan plots for life satisfaction analysis, positive affect analysis, and post hoc subjective well-being analysis using 1000 Genomes Project SNPs.

  6. 6.

    LocusZoom plots for reference SNPs rs13185787 and r6579956.

  7. 7.

    Quantile–quantile plots for depressive symptoms and neuroticism GWAS.

  8. 8.

    LD Score regression plots based on the summary statistics from the GWAS of subjective well-being, depressive symptoms, and neuroticism.

  9. 9.

    Power of the sign test.

  10. 10.

    Histograms of the principal components tagging the inversions on chromosomes 8 and 17.

  11. 11.

    Squared correlations between each SNP on chromosome 8 and the principal component tagging the inversion on chromosome 8.

  12. 12.

    Local Manhattan plot for chromosome 17 (above horizontal line) and squared correlations between each SNP on chromosome 17 and the principal component tagging the inversion on chromosome 17 (below horizontal line).

  13. 13.

    Associations between inversion-tagging SNPs on chromosome 8 and neuroticism and subjective well-being.

  14. 14.

    Posterior credibility of GWAS results.

  15. 15.

    Polygenic score prediction in HRS and NTR.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–15 and Supplementary Note.

Excel files

  1. 1.

    Supplementary Tables 1–35

    Supplementary Tables 1–35.