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Nat Genet. 2016 Jun;48(6):624-33. doi: 10.1038/ng.3552. Epub 2016 Apr 18.

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

Okbay A1,2,3, Baselmans BM4,5, De Neve JE6, Turley P7, Nivard MG4, Fontana MA8, Meddens SF3,9,10, Linnér RK3,9,10, Rietveld CA1,2,3, Derringer J11, Gratten J12, Lee JJ13, Liu JZ14, de Vlaming R1,2,3, Ahluwalia TS15,16,17, Buchwald J18, Cavadino A19,20, Frazier-Wood AC21, Furlotte NA22, Garfield V23, Geisel MH24, Gonzalez JR25,26,27, Haitjema S28, Karlsson R29, van der Laan SW28, Ladwig KH30, Lahti J31,32,33, van der Lee SJ2, Lind PA34, Liu T35,36, Matteson L13, Mihailov E37, Miller MB13, Minica CC4, Nolte IM38, Mook-Kanamori D39,40,41, van der Most PJ38, Oldmeadow C42,43, Qian Y44, Raitakari O45,46, Rawal R47, Realo A48,49, Rueedi R50,51, Schmidt B24, Smith AV52,53, Stergiakouli E54, Tanaka T55, Taylor K56, Thorleifsson G, Wedenoja J18, Wellmann J57, Westra HJ58,59, Willems SM2, Zhao W60; LifeLines Cohort Study, Amin N2, Bakshi A12, Bergmann S, Bjornsdottir G, Boyle PA61, Cherney S62, Cox SR63,64, Davies G63,64, Davis OS54, Ding J44, Direk N2, Eibich P65,66, Emeny RT67,68, Fatemifar G69, Faul JD70, Ferrucci L55, Forstner AJ71,72, Gieger C47, Gupta R18, Harris TB73, Harris JM74, Holliday EG42,43, Hottenga JJ4,5, De Jager PL75,76,77, Kaakinen MA78,79, Kajantie E80,81, Karhunen V79, Kolcic I82, Kumari M83, Launer LJ84, Franke L85, Li-Gao R39, Liewald DC, Koini M86, Loukola A18, Marques-Vidal P87, Montgomery GW88, Mosing MA89, Paternoster L54, Pattie A64, Petrovic KE86, Pulkki-Råback L31,33, Quaye L74, Räikkönen K31, Rudan I90, Scott RJ43,91, Smith JA60, Sutin AR55,92, Trzaskowski M12,82, Vinkhuyzen AE12, Yu L93, Zabaneh D82, Attia JR42,43, Bennett DA93, Berger K57, Bertram L94,95, Boomsma DI4,5,96, Snieder H38, Chang SC97, Cucca F98, Deary IJ63,64, van Duijn CM2, Eriksson JG99,100,101, Bültmann U102, de Geus EJ4,5,96, Groenen PJ3,103, Gudnason V52,53, Hansen T16, Hartman CA104, Haworth CM54, Hayward C105, Heath AC106, Hinds DA22, Hyppönen E20,107,108, Iacono WG13, Järvelin MR78,109,110,111, Jöckel KH24, Kaprio J18,112,113, Kardia SL60, Keltikangas-Järvinen L31, Kraft P114, Kubzansky LD115, Lehtimäki T116,117, Magnusson PK29, Martin NG118, McGue M13, Metspalu A37,119, Mills M120, de Mutsert R39, Oldehinkel AJ103, Pasterkamp G28,121, Pedersen NL29, Plomin R122, Polasek O82, Power C20,108, Rich SS123, Rosendaal FR39, den Ruijter HM28, Schlessinger D44, Schmidt H86,124, Svento R125, Schmidt R86, Alizadeh BZ38,126, Sørensen TI16,54,127, Spector TD74, Starr JM, Stefansson K, Steptoe A23, Terracciano A55,92, Thorsteinsdottir U, Thurik AR1,3,128,129, Timpson NJ54, Tiemeier H2,130,131, Uitterlinden AG2,3,132, Vollenweider P87, Wagner GG35,65,133, Weir DR70, Yang J12,134, Conley DC135, Smith GD54, Hofman A2,136, Johannesson M137, Laibson DI7, Medland SE34, Meyer MN138,139, Pickrell JK14,140, Esko T37, Krueger RF13, Beauchamp JP7, Koellinger PD3,9,10, Benjamin DJ8, Bartels M4,5,96, Cesarini D141,142.

Author information

1
Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
2
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
3
Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.
4
Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
5
EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands.
6
Saïd Business School, University of Oxford, Oxford, UK.
7
Department of Economics, Harvard University, Cambridge, Massachusetts, USA.
8
Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
9
Department of Complex Trait Genetics, Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands.
10
Amsterdam Business School, University of Amsterdam, Amsterdam, the Netherlands.
11
Department of Psychology, University of Illinois, Champaign, Illinois, USA.
12
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
13
Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
14
New York Genome Center, New York, New York, USA.
15
COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
16
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
17
Steno Diabetes Center, Gentofte, Denmark.
18
Department of Public Health, University of Helsinki, Helsinki, Finland.
19
Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
20
South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
21
USDA-ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.
22
23andMe, Inc., Mountain View, California, USA.
23
Department of Epidemiology and Public Health, University College London, London, UK.
24
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany.
25
Centre for Research in Environmental Epidemiology, Institute for Global Health, Barcelona, Spain.
26
Universitat Pompeu Fabra, Barcelona, Spain.
27
CIBER Epidemiología y Salud Pública, Barcelona, Spain.
28
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
29
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
30
Department of Psychosomatic Medicine and Psychotherapy, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
31
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
32
Folkhälsan Research Centre, Helsingfors, Finland.
33
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
34
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
35
Max Planck Institute for Human Development, Berlin, Germany.
36
Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany.
37
Estonian Genome Center, University of Tartu, Tartu, Estonia.
38
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
39
Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
40
Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
41
BESC, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
42
Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
43
Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
44
Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.
45
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
46
Department of Clinical Physiology, Turku University Hospital, Turku, Finland.
47
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
48
Department of Psychology, University of Tartu, Tartu, Estonia.
49
Department of Psychology, University of Warwick, Coventry, UK.
50
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
51
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
52
Icelandic Heart Association, Kopavogur, Iceland.
53
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
54
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
55
National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.
56
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA, Torrence, California, USA.
57
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
58
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
59
Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
60
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
61
Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.
62
RAND Corporation, Santa Monica, California, USA.
63
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
64
Department of Psychology, University of Edinburgh, Edinburgh, UK.
65
German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany.
66
Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
67
Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
68
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
69
Farr Institute of Health Informatics, University College London, London, UK.
70
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
71
Institute of Human Genetics, University of Bonn, Bonn, Germany.
72
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
73
Laboratory of Epidemiology, Demography, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
74
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
75
Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
76
Harvard Medical School, Boston, Massachusetts, USA.
77
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
78
Department of Genomics of Common Disease, Imperial College London, London, UK.
79
Center for Life Course Health Research, University of Oulu and Oulu University Hospital, Oulu, Finland.
80
Department of Pediatrics, University of Helsinki, Helsinki, Finland.
81
National Institute for Health and Welfare, Helsinki, Finland.
82
Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
83
Institute for Social and Economic Research, University of Essex, Wivenhoe Park, UK.
84
Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
85
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
86
Department of Neurology, General Hospital and Medical University Graz, Graz, Austria.
87
Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
88
Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
89
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
90
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
91
Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
92
Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, Florida, USA.
93
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
94
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institute of Neurogenetics and Institute of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
95
Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
96
Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
97
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
98
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitarià di Monserrato, Monserrato, Italy.
99
Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
100
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
101
Unit of General Practice, University Central Hospital, Helsinki, Finland.
102
Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
103
Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.
104
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
105
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
106
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
107
Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia.
108
Population, Policy and Practice, UCL Institute of Child Health, London, UK.
109
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
110
Biocenter Oulu, University of Oulu, Oulu, Finland.
111
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
112
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
113
Department for Health, THL (National Institute for Health and Welfare), Helsinki, Finland.
114
Department of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
115
Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
116
Fimlab Laboratories, Tampere, Finland.
117
Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland.
118
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
119
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
120
Department of Sociology, University of Oxford, Oxford, UK.
121
Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.
122
Social, Genetic and Developmental Psychiatry Centre, King's College London, De Crespigny Park, UK.
123
Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
124
Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University Graz, Graz, Austria.
125
Department of Economics, Oulu Business School, Oulu, Finland.
126
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
127
Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, Capital Region, Frederiksberg, Denmark.
128
Montpellier Business School, Montpellier, France.
129
Panteia, Zoetermeer, the Netherlands.
130
Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.
131
Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.
132
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
133
School of Economics and Management, Berlin University of Technology, Berlin, Germany.
134
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
135
Department of Sociology, Princeton University, Princeton, New Jersey, USA.
136
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
137
Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
138
Department of Bioethics, Clarkson University, Schenectady, New York, USA.
139
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
140
Department of Biological Sciences, Columbia University, New York, New York, USA.
141
Department of Economics, New York University, New York, New York, USA.
142
Research Institute for Industrial Economics, Stockholm, Sweden.

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.

PMID:
27089181
PMCID:
PMC4884152
DOI:
10.1038/ng.3552
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing Financial Interests: The authors declare no competing financial interests.

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