期刊
MOLECULAR PSYCHIATRY
卷 17, 期 1, 页码 36-48出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2010.109
关键词
major depressive disorder; depression; genome-wide association study; CACNA1C; ADCY3; GAL
资金
- Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613608]
- FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]
- US National Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951]
- Netherlands Scientific Organization (NWO) [480-05-003]
- National Health and Medical Research Council
- Australian Research Council
- Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05-717]
- Neuroscience Campus Amsterdam and the EMGO+ institute
- European Union [EU/WLRT-2001-01254]
- ZonMW (Geestkracht program) [10-000-1002]
- National Institute of Mental Health Schizophrenia (NIMH) [RO1 MH059160, MH080403]
- NESDA
- NTR
- Wellcome Trust, London
- Chief Scientist Office of the Scottish Government
- [NWO-SPI 56-464-1419]
- Medical Research Council [G0701420, G9817803B] Funding Source: researchfish
- MRC [G0701420] Funding Source: UKRI
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH059586, R01MH080403, R01MH061675, R01MH059565, R01MH066206, R01MH059160, R01MH060879, R01MH059571, R01MH059566, R01MH067257, R01MH060870, R01MH059587, R01MH059588] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA014041, K05AA017688, R01AA007535, R01AA013320, R01AA013321, R01AA013326] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K08DA019951, R01DA012854, R56DA012854] Funding Source: NIH RePORTER
Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P = 0.020, odds ratio = 1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P = 0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD. Molecular Psychiatry (2012) 17, 36-48; doi:10.1038/mp.2010.109; published online 2 November 2010
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