期刊
BIOLOGICAL PSYCHIATRY
卷 73, 期 7, 页码 667-678出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2012.09.033
关键词
Center for Epidemiologic Studies Depression Scale; CHARGE consortium; depression; depressive symptoms; genetics; genome-wide association study; meta-analysis
资金
- Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
- National Institutes of Health (NIH) [N01-AG-12100, HHSN268200625226C, UL1RR025005, HHSN268200782096C, R01 MH086498, CA65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233]
- NIA
- Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL087641, R01-HL093029, R01-HL70825]
- National Human Genome Research Institute [U01-HG004402]
- NIH Roadmap for Medical Research
- NIH, National Institute on Aging [NO1-AG-1-2109]
- NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756, N01-HC-25195, N02-HL-6-4278, N01-HC-65226]
- NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, R01AG15819, R01AG17917, K08AG34290, P30AG10161, R01AG30146]
- Clinical and Translational Science Institute [UL1RR033176]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- European Community
- European Network for Genetic and Genomic Epidemiology Consortium [HEALTHF-4-2007- 201413]
- European Special Populations Research Network
- European Commission [018947, LSHG-CT-2006-01947]
- Netherlands Organisation for Scientific Research, Erasmus MC
- Centre for Medical Systems Biology
- Netherlands Brain Foundation (HersenStichting Nederland)
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
- Boston Medical Center
- Academy of Finland
- Finnish Diabetes Research Society
- Folkhalsan Research Foundation
- Novo Nordisk Foundation
- Finska Lakaresallskapet
- Signe and Ane Gyllenberg Foundation
- University of Helsinki
- European Science Foundation (EUROSTRESS)
- Ministry of Education
- Ahokas Foundation
- Emil Aaltonen Foundation
- Juho Vainio Foundation
- Wellcome Trust [WT098051]
- Italian Ministry of Health [ICS 110.1RS97.71]
- U.S. National Institute on Aging [N01]AG]916413, N01]AG]821336, 263 MD 9164 13, 263 MD 821336]
- Helmholtz Zentrum Munchen
- German Research Center for Environmental Health, Neuherberg, Germany
- German Federal Ministry of Education and Research
- Munich Center of Health Sciences as part of Ludwig-Maximilians-University
- Netherlands Organisation of Scientific Research Investments [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research [050-060-810]
- Erasmus MC
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (Directorate-General XII)
- Municipality of Rotterdam
- Vidi Grant of Netherlands Organization for the Health Research and Development [2009-017.106.370]
- BavoEuropoort
- German Bundesministerium fur Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]
- Translational Genomics Research Institute
- Burroughs Wellcome Fund
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- German Research Foundation (DFG) [GR 1912/5-1]
- Federal Ministry of Education and Research Germany
- Humboldt Foundation
- German Research Foundation
- Lundbeck
- Janssen-Cilag
- Eli Lilly
- Novartis
- AstraZeneca
- SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health
- Sanofi-Aventis
- Biotronik
- [R01-AG29451]
- [N01-HC-95159]
- [N01-HC-95169]
- [UL1-RR-024156]
- [R01 HL101161]
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 x 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 x 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 x 10(-3)). This 5q21 region reached genome-wide significance (p = 4.78 x 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.
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