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

  • 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
  • , Jaime Derringer
  • , Jacob Gratten
  • , James J. Lee
  • , Jimmy Z. Liu
  • , Ronald De Vlaming
  • , Tarunveer SAhluwalia
  • , Jadwiga Buchwald
  • , Alana Cavadino
  • , Alexis C. Frazier-Wood
  • , Nicholas A. Furlotte
  • , Victoria Garfield
  • Marie Henrike Geisel, Juan R. Gonzalez, Saskia Haitjema, Robert Karlsson, Sander Wvan Der Laan, Karl Heinz Ladwig, Jari Lahti, Sven J. Van Der Lee, Penelope A. Lind, Tian Liu, Lindsay Matteson, Evelin Mihailov, Michael B. Miller, Camelia CMinica, Ilja MNolte, Dennis Mook-Kanamori, Peter J. Van Der Most, Christopher Oldmeadow, Yong Qian, Olli Raitakari, Rajesh Rawal, Anu Realo, Rico Rueedi, Börge Schmidt, Albert V. Smith, Evie Stergiakouli, Toshiko Tanaka, Kent Taylor, Juho Wedenoja, Juergen Wellmann, Harm Jan Westra, Sara MWillems, Wei Zhao, Life Lines Cohort Study, Najaf Amin, Andrew Bakshi, Patricia A. Boyle, Samantha Cherney, Simon R. Cox, Gail Davies, Oliver S.P. Davis, Jun Ding, Nese Direk, Peter Eibich, Rebecca T. Emeny, Ghazaleh Fatemifar, Jessica D. Faul, Luigi Ferrucci, Andreas Forstner, Christian Gieger, Richa Gupta, Tamara B. Harris, Juliette M. Harris, Elizabeth G. Holliday, Jouke Jan Hottenga, Philip L. De Jager, Marika A. Kaakinen, Eero Kajantie, Ville Karhunen, Ivana Kolcic, Meena Kumari, Lenore J. Launer, Lude Franke, Ruifang Li-Gao, Marisa Koini, Anu Loukola, Pedro Marques-Vidal, Grant W. Montgomery, Miriam A. Mosing, Lavinia Paternoster, Alison Pattie, Katja E. Petrovic, Laura Pulkki-R'back, Lydia Quaye, Katri R'ikkönen, Igor Rudan, Rodney J. Scott, Jennifer A. Smith, Angelina R. Sutin, Maciej Trzaskowski, Anna E. Vinkhuyze, Lei Yu, Delilah Zabaneh, John R. Attia, David A. Bennett, Klaus Berger, Lars Bertram, Dorret I. Boomsma, Harold Snieder, Shun Chiao Chang, Francesco Cucca, Ian J. Deary, Cornelia M. Van Duijn, Johan G. Eriksson, Ute Bültmann, Eco J.Cde Geus, Patrick J.F. Groenen, Vilmundur Gudnason, Torben Hansen, Catharine A. Hartman, Claire M.A. Haworth, Caroline Hayward, Andrew C. Heath, David A. Hinds, Elina Hyppönen, William G. Iacono, Marjo Riitta J'rvelin, Karl Heinz Jöckel, Jaakko Kaprio, Sharon L.R. Kardia, Liisa Keltikangas-J'rvinen, Peter Kraft, Laura D. Kubzansky, Terho Lehtim'ki, Patrik K.E. Magnusson, Nicholas G. Martin, Matt McGue, Andres Metspalu, Melinda Mills, Renée De Mutsert, Albertine J. Oldehinkel, Gerard Pasterkamp, Nancy L. Pedersen, Robert Plomin, Ozren Polasek, Christine Power, Stephen S. Rich, Frits R. Rosendaal, Hester M. Den Ruijter, David Schlessinger, Helena Schmidt, Rauli Svento, Reinhold Schmidt, Behrooz Z. Alizadeh, Thorkild I.A. SØrensen, Tim DSpector, Andrew Steptoe, Antonio Terracciano, A. Roy Thurik, Nicholas J. Timpson, Henning Tiemeier, André G. Uitterlinden, Peter Vollenweider, Gert G. Wagner, David R. Weir, Jian Yang, Dalton C. Conley, George Davey Smith, Albert Hofman, Magnus Johannesson, David I. Laibson, Sarah E. Medland, Michelle N. Meyer, Joseph K. Pickrell, T'nu Esko, Robert F. Krueger, Jonathan P. Beauchamp, Philipp D. Koellinger*, Daniel J. Benjamin, Meike Bartels, David Cesarini
*Corresponding author for this work
  • Erasmus University Rotterdam
  • Vrije Universiteit Amsterdam
  • University of Amsterdam
  • University of Oxford
  • Harvard University
  • University of Southern California
  • University of Illinois at Urbana-Champaign
  • University of Queensland
  • University of Minnesota Twin Cities
  • New York Genome Center
  • University of Copenhagen
  • Novo Nordisk Foundation
  • University of Helsinki
  • Queen Mary University of London
  • South Australian Health And Medical Research Institute
  • Baylor College of Medicine
  • Me Inc.
  • University College London
  • University of Duisburg-Essen
  • Barcelona Institute for Global Health
  • Pompeu Fabra University
  • Biomedical Research Networking Center in Epidemiology and Public Health (CiberESP)
  • Utrecht University
  • Karolinska Institutet
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Technical University of Munich
  • Folkh'lsan Research Centre
  • Queensland Institute of Medical Research
  • Max Planck Institute for Human Development
  • Max Planck Institute for Molecular Genetics
  • University of Tartu
  • University of Groningen
  • Leiden University
  • King Faisal Specialist Hospital and Research Centre
  • Hunter Medical Research Institute, Australia
  • University of Newcastle
  • National Institutes of Health
  • University of Turku
  • University of Tartu
  • University of Warwick
  • University of Lausanne
  • Swiss Institute of Bioinformatics
  • Icelandic Heart Association
  • University of Iceland
  • University of Bristol
  • The Lundquist Institute
  • University of Münster
  • Brigham and Women’s Hospital
  • University of Michigan, Ann Arbor
  • Rush University Medical Center
  • RAND Corporation
  • University of Edinburgh
  • German Institute for Economic Research
  • Dartmouth College
  • University of Bonn
  • King's College London
  • Broad Institute
  • Imperial College London
  • University of Oulu
  • National Institute for Health and Welfare
  • University of Split
  • University of Essex
  • Medical University of Graz
  • Florida State University
  • University of Lübeck
  • National Research Council of Italy
  • Helsinki University Hospital
  • Washington University St. Louis
  • Adelaide University
  • Fimlab Laboratories
  • Tampere University
  • University of Virginia
  • Montpellier Business School
  • Panteia
  • Technical University of Berlin
  • Princeton University
  • Stockholm School of Economics
  • Clarkson University
  • Icahn School of Medicine at Mount Sinai
  • Columbia University
  • New York University
  • Research Institute for Industrial Economics

Research output: Contribution to journalArticlepeer-review

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 (P = 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.

Original languageEnglish
Pages (from-to)624-633
Number of pages10
JournalNature Genetics
Volume48
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016
Externally publishedYes

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