title: Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.
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.
authors.affiliation: 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.
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authors.affiliation: Department of Economics, Harvard University, Cambridge, Massachusetts, USA.
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authors.affiliation: Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
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authors.identifier: 0000-0003-2015-1888
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authors.affiliation: 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.
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authors.lastname: Meddens
authors.affiliation: 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.
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authors.initials: RK
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authors.affiliation: 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.
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authors.identifier: 0000-0001-6547-5128
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.identifier: 0000-0002-5159-8802
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authors.affiliation: Department of Neurology, General Hospital and Medical University Graz, Graz, Austria.
authors.forename: Marisa
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authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
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authors.initials: GW
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authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
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authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.|Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
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authors.identifier: 0000-0001-6993-6884
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authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
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authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
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authors.affiliation: Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
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authors.affiliation: 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.
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authors.identifier: 0000-0001-9800-1308
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authors.affiliation: Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
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authors.affiliation: 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.
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitarià di Monserrato, Monserrato, Italy.
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authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.affiliation: 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.
authors.forename: Johan G
authors.initials: JG
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authors.affiliation: Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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authors.lastname: Bültmann
authors.affiliation: 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.
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authors.identifier: 0000-0001-6022-2666
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authors.affiliation: Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.|Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Patrick J F
authors.initials: PJ
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
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authors.initials: CM
authors.lastname: Haworth
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Andrew C
authors.initials: AC
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authors.affiliation: 23andMe, Inc., Mountain View, California, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: 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.
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
authors.affiliation: Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
authors.forename: William G
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authors.initials: MR
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authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany.
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authors.initials: KH
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authors.affiliation: 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.
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authors.identifier: 0000-0002-3716-2455
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authors.affiliation: Fimlab Laboratories, Tampere, Finland.|Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
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authors.initials: A
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authors.affiliation: Department of Sociology, University of Oxford, Oxford, UK.
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authors.affiliation: Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
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authors.affiliation: 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.
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authors.initials: C
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authors.affiliation: Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.identifier: 0000-0002-1415-8007
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authors.affiliation: 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.
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authors.initials: TI
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authors.initials: A
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authors.affiliation: 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.
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authors.initials: A
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authors.forename: Unnur
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authors.affiliation: 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.
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authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
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authors.affiliation: 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.
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authors.identifier: 0000-0002-4395-1397
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authors.affiliation: 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.
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authors.initials: P
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authors.affiliation: 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.
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authors.initials: GG
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authors.initials: DR
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authors.identifier: 0000-0003-2001-2474
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authors.initials: A
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authors.affiliation: Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
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authors.affiliation: Department of Bioethics, Clarkson University, Schenectady, New York, USA.|Icahn School of Medicine at Mount Sinai, New York, New York, USA.
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authors.affiliation: New York Genome Center, New York, New York, USA.|Department of Biological Sciences, Columbia University, New York, New York, USA.
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authors.initials: JK
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
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authors.affiliation: 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.
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authors.initials: PD
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authors.affiliation: Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
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authors.initials: DJ
authors.lastname: Benjamin
authors.affiliation: 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.
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mesh_terms: D001008:Anxiety Disorders / Q000235:genetics*; D001499:Bayes Theorem; D003863:Depression / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D000075384:Neuroticism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide