Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies
Year: 2016
Type: review
Abstract: BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Source: Psychological Medicine
Authors: A. Demirkan, J. Lahti, N. Direk, A. Viktorin, K. L. Lunetta, A. Terracciano, M. A. Nalls, T. Tanaka, K. Hek, M. Fornage, J. Wellmann, M. C. Cornelis, H. M. Ollila, L. Yu, J. A. Smith, L. C. Pilling, A. Isaacs, A. Palotie, W. V. Zhuang, A. Zonderman, J. D. Faul, A. Sutin, O. Meirelles, A. Mulas, A. Hofman, A. Uitterlinden, F. Rivadeneira, M. Perola, W. Zhao, V. Salomaa, K. Yaffe, A. I. Luik, NABEC, UKBEC, Y. Liu, J. Ding, P. Lichtenstein, M. Landén, E. Widen, D. R. Weir, D. J. Llewellyn, A. Murray, S. L. R. Kardia, J. G. Eriksson, K. Koenen, P. K. E. Magnusson, L. Ferrucci, T. H. Mosley, F. Cucca, B. A. Oostra, D. A. Bennett, T. Paunio, K. Berger, T. B. Harris, N. L. Pedersen, J. M. Murabito, H. Tiemeier, C. M. van Duijn, K. Räikkönen
Institutions: Erasmus MC, University of Helsinki, Karolinska Institutet, Boston University, Florida State University, National Institutes of Health, National Institute on Aging, University of Münster, Brigham and Women's Hospital, Harvard University, Finnish Institute for Health and Welfare, Institute for Molecular Medicine Finland, Rush University Medical Center, University of Michigan, University of Exeter, Wellcome Sanger Institute, Creighton University, Institute for Social Research, Institute of Genetic and Biomedical Research, Netherlands Consortium for Healthy Ageing, University of California, San Francisco, Wake Forest University, Wake Forest University Health Sciences, Columbia University, University of Mississippi Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Illinois Department of Public Health, Wake Forest University, Wellcome Trust, National Institute for Health and Care Research, Centre for Medical Systems Biology, National Institutes of Health, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Center for Research Resources
Awards: Characterization of Normal Genomic Variability, Epidemiologic Study of Neural Reserve and Neurobiology of Aging, Genetic Determinants of Visceral Adiposity, G1325221871, DYNAMICS OF HEALTH,AGING, AND BODY COMPOSITION, G2070131968, Atherosclerosis Risk in Communities Study (ARIC), DYNAMICS OF HEALTH, AGING, AND BODY COMPOSITION, Institute for Clinical and Translational Research (UL1), CCSP FIELD CENTER, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, Exceptional Aging Across the Life Span: Framingham Study, HEALTH ABC--COORDINATING UNIT, G3236609591, G36937976, G3700906957, GWA for Gene-Environment Interaction Effects Influencing CHD, G390162502, Creating a National Resource for Genetic Research in Behavioral & Health Sciences, Atherosclerosis Risk in Communities Study (ARIC), G4855546878, Risk Factors, Pathology, and Clinical Expressions of AD, Rush Alzheimer's Disease Core Center, G5164707915, Characterization of Normal Genomic Variability, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5451084504, Atherosclerosis Risk in Communities Study (ARIC), A Genome-Wide Association Study of Ischemic Brain Vascular Injury, G5909482378, G6203107232, The Framingham Heart Study, SNP HEALTH ASSOCIATION RESOURCE (SHARE), G7423759087, The ARIC and Neurocognitive Longitudinal Study, G812579647, G8267674335, REDUCING SERVICE USE IN OLDER PRIMARY CARE PATIENTS, G8486527673, G870807107, Health and Retirement Study: Yrs 35-40, G945304896, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2308529582