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 S Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-Wood, Nicholas A Furlotte, Victoria Garfield, Marie Henrike Geisel, Juan R Gonzalez, Saskia Haitjema, Robert Karlsson, Sander W van 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 C Minica, Ilja M Nolte, 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, Gudmar Thorleifsson, Juho Wedenoja, Juergen Wellmann, Harm-Jan Westra, Sara M Willems, Wei Zhao, Najaf Amin, Andrew Bakshi, Sven Bergmann, Gyda Bjornsdottir, 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 J 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, David C Liewald, Marisa Koini, Anu Loukola, Pedro Marques-Vidal, Grant W Montgomery, Miriam A Mosing, Lavinia Paternoster, Alison Pattie, Katja E Petrovic, Laura Pulkki-Råback, Lydia Quaye, Katri Räikkönen, Igor Rudan, Rodney J Scott, Jennifer A Smith, Angelina R Sutin, Maciej Trzaskowski, Anna E Vinkhuyzen, 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 C de 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 Järvelin, Karl-Heinz Jöckel, Jaakko Kaprio, Sharon L R Kardia, Liisa Keltikangas-Järvinen, Peter Kraft, Laura D Kubzansky, Terho Lehtimäki, 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 D Spector, John M Starr, Kari Stefansson, Andrew Steptoe, Antonio Terracciano, Unnur Thorsteinsdottir, 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, Tõnu Esko, Robert F Krueger, Jonathan P Beauchamp, Philipp D Koellinger, Daniel J Benjamin, Meike Bartels, David Cesarini

Journal: Nature genetics 2017;48(6):624-33

PMID: 27089181

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.

Address: Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.; EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.; Saïd Business School, University of Oxford, Oxford, UK.; Department of Economics, Harvard University, Cambridge, Massachusetts, USA.; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.; Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.; Department of Complex Trait Genetics, Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands.; Amsterdam Business School, University of Amsterdam, Amsterdam, the Netherlands.; Department of Psychology, University of Illinois, Champaign, Illinois, USA.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.; New York Genome Center, New York, New York, USA.; COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Steno Diabetes Center, Gentofte, Denmark.; Department of Public Health, University of Helsinki, Helsinki, Finland.; Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; USDA-ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.; 23andMe, Inc., Mountain View, California, USA.; Department of Epidemiology and Public Health, University College London, London, UK.; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany.; Centre for Research in Environmental Epidemiology, Institute for Global Health, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública, Barcelona, Spain.; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Psychosomatic Medicine and Psychotherapy, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.; Folkhälsan Research Centre, Helsingfors, Finland.; Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Max Planck Institute for Human Development, Berlin, Germany.; Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany.; Estonian Genome Center, University of Tartu, Tartu, Estonia.; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.; BESC, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.; Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.; Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.; Department of Clinical Physiology, Turku University Hospital, Turku, Finland.; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.; Department of Psychology, University of Tartu, Tartu, Estonia.; Department of Psychology, University of Warwick, Coventry, UK.; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland.; Icelandic Heart Association, Kopavogur, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.; Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA, Torrence, California, USA.; Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.; Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.; RAND Corporation, Santa Monica, California, USA.; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.; Department of Psychology, University of Edinburgh, Edinburgh, UK.; German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany.; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.; Farr Institute of Health Informatics, University College London, London, UK.; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.; Laboratory of Epidemiology, Demography, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.; Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.; Department of Genomics of Common Disease, Imperial College London, London, UK.; Center for Life Course Health Research, University of Oulu and Oulu University Hospital, Oulu, Finland.; Department of Pediatrics, University of Helsinki, Helsinki, Finland.; National Institute for Health and Welfare, Helsinki, Finland.; Center for Life Course Health Research, University of Oulu and Oulu University Hospital, Oulu, Finland.; Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.; Institute for Social and Economic Research, University of Essex, Wivenhoe Park, UK.; Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Neurology, General Hospital and Medical University Graz, Graz, Austria.; Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.; Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Department of Psychology, University of Edinburgh, Edinburgh, UK.; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.; Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.; Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.; Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.; National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.; Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, Florida, USA.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.; Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institute of Neurogenetics and Institute of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.; EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.; Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitarià di Monserrato, Monserrato, Italy.; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.; Unit of General Practice, University Central Hospital, Helsinki, Finland.; Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.; Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.; Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia.; Population, Policy and Practice, UCL Institute of Child Health, London, UK.; Department of Genomics of Common Disease, Imperial College London, London, UK.; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Unit of Primary Care, Oulu University Hospital, Oulu, Finland.; Department of Public Health, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Department for Health, THL (National Institute for Health and Welfare), Helsinki, Finland.; Department of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Fimlab Laboratories, Tampere, Finland.; Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland.; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Estonian Genome Center, University of Tartu, Tartu, Estonia.; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.; Department of Sociology, University of Oxford, Oxford, UK.; Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.; Social, Genetic and Developmental Psychiatry Centre, King's College London, De Crespigny Park, UK.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Population, Policy and Practice, UCL Institute of Child Health, London, UK.; Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.; Department of Neurology, General Hospital and Medical University Graz, Graz, Austria.; Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University Graz, Graz, Austria.; Department of Economics, Oulu Business School, Oulu, Finland.; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, Capital Region, Frederiksberg, Denmark.; Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.; Montpellier Business School, Montpellier, France.; Panteia, Zoetermeer, the Netherlands.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.; Max Planck Institute for Human Development, Berlin, Germany.; German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany.; School of Economics and Management, Berlin University of Technology, Berlin, Germany.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.; Department of Sociology, Princeton University, Princeton, New Jersey, USA.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Department of Economics, Stockholm School of Economics, Stockholm, Sweden.; Department of Bioethics, Clarkson University, Schenectady, New York, USA.; Icahn School of Medicine at Mount Sinai, New York, New York, USA.; New York Genome Center, New York, New York, USA.; Department of Biological Sciences, Columbia University, New York, New York, USA.; Department of Economics, New York University, New York, New York, USA.; Research Institute for Industrial Economics, Stockholm, Sweden.
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