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BACKGROUND:Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS:In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. RESULTS:The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258). CONCLUSIONS:The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.

Original publication




Journal article


Biological psychiatry

Publication Date





667 - 678


Research Centre O3 (KH, CLM, HT), Department of Psychiatry, and Department of Epidemiology (KH, AH, MK, AGU, HT), Erasmus MC, Rotterdam, The Netherlands; Institute of Behavioural Sciences (JL, KRa), University of Helsinki, Helsinki, Finland; Clinical Research Branch (TT), National Institute on Aging, Baltimore, Maryland; Interfaculty Institute for Genetics and Functional Genomics (ATeu), University Medicine Greifswald, Greifswald, Germany; Department of Nutrition (MCC, FBH, EBR, MKJ), Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology (EB, AVD-R, SK), University of Michigan School of Public Health, Ann Arbor, Michigan; Institute of Epidemiology II (JB, RE, K-HL), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Internal Medicine (JD), Division of Geriatrics, and Department of Epidemiology and Prevention (YL), Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina; Department of Medicine (KM), Cardiovascular Health Research Unit, University of Washington, Seattle, Washington; National Institute on Aging (ATer, OM, ARS), National Institutes of Health, Department of Health and Human Services, Baltimore; and Laboratory of Neurogenetics (MAN, ABS), Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Department of Epidemiology (YVS), Emory University, Atlanta, Georgia; EMGO Institute for Health and Care Research (NV, BPe), and Department of Psychiatry (NV, BPe), VU University Medical Center, Amsterdam, The Netherlands; Rush Alzheimer's Disease Center (LY, DAB), and Department of Neurological Sciences (LY, DAB), Rush University Medical Center, Chicago, Illinois; Geriatric Unit Azienda Sanitaria di Firenze (SB), Firenze, Italy; National Heart, Lung, and Blood Institute's Framingham Heart Study (EJB, MK-H, JMM, KLL, JM), Framingham; and Department of Medicine (EJB), Section of Cardiology and Preventive Medicine, Boston University School of Medicine and Public Health, Boston, Massachusetts; Department of Biological Psychology (DB, EdG), VU University, Amsterdam, The Netherlands; Istituto di Ricerca Genetica e Biomedica (AC, AMul, FC), Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy; Division of Public Health Sciences (LHC), Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Neurology (PLDJ), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Psychiatry (SP), Massachusetts General Hospital and Harvard Medical School, Boston, and the Broad Institute, Cambridge; and Department of Epidemiology (FBH, EBR), Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics (KRi), University of Washington, Seattle, Washington; Center of Biostatistics and Department of Medicine (ADP), University of Mississippi Medical Center, Jackson, Mississippi; Medical Genetics Institute (JIR), Cedars Sinai Medical Center, Los Angeles, California; Division of Cardiology (NS), and Cardiovascular Health Research Unit (NS), Department of Medicine, University of Washington, Seattle, Washington; National Institute for Health and Welfare (JGE); Department of General Practice and Primary Health Care (JGE), University of Helsinki; Unit of General Practice (JGE), Helsinki University Central Hospital; and Folkhalsan Research Centre (JGE), Helsinki; and Vasa Central Hospital (JGE), Vasa, Finland; Department of Internal Medicine (DAE), Rush Institute for Health Aging, Rush University Medical Center, Chicago, Illinois; Longitudinal Studies Section (LF), Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland; Brown Foundation Institute of Molecular Medicine (MF), University of Texas Health Science Center at Houston, Houston, Texas; Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healt


Chromosomes, Human, Pair 5, Humans, Genetic Predisposition to Disease, Depression, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study