@article{3a638d6748ea44d9a53eed4d278914a5,
title = "Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned",
abstract = "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 1 M 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 (P0.020, odds ratio1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P0.51). 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.",
keywords = "ADCY3, CACNA1C, GAL, depression, genome-wide association study, major depressive disorder",
author = "Wray, {N. R.} and Pergadia, {M. L.} and Blackwood, {D. H.R.} and Penninx, {B. W.J.H.} and Gordon, {S. D.} and Nyholt, {D. R.} and S. Ripke and MacIntyre, {D. J.} and McGhee, {K. A.} and MacLean, {A. W.} and Smit, {J. H.} and Hottenga, {J. J.} and G. Willemsen and Middeldorp, {C. M.} and {De Geus}, {E. J.C.} and Lewis, {C. M.} and P. McGuffin and Hickie, {I. B.} and {Van Den Oord}, {E. J.C.G.} and Liu, {J. Z.} and S. MacGregor and McEvoy, {B. P.} and Byrne, {E. M.} and Medland, {S. E.} and Statham, {D. J.} and Henders, {A. K.} and Heath, {A. C.} and Montgomery, {G. W.} and Martin, {N. G.} and Boomsma, {D. I.} and Madden, {P. A.F.} and Sullivan, {P. F.}",
note = "Funding Information: Funding support was provided by the Netherlands Scientific Organization (904-61-090, 904-61-193, 480-04-004, 400-05-717, Centre for Medical Systems Biology (NWO Genomics), the Neuroscience Campus Amsterdam and the EMGO + institute; the European Union (EU/WLRT-2001-01254), ZonMW (Geestkracht program, 10-000-1002), NIMH (RO1 MH059160) and matching funds from participating institutes in NESDA and NTR. The NTR controls were genotyped in the Genomics platform (certified service provider (CSPro(R)) for Illumina) at the LIFE and BRAIN Center Bonn (funded by NWO-SPI 56-464-1419). Funding Information: Smyth, Harry Beeby, and Daniel Park (IT support). Funding was provided by the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613608), the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254), and the US National Institutes of Health (NIH grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951). A portion of the genotyping on which this study was based (Illumina 370K scans on 4300 individuals) was carried out at the Center for Inherited Disease Research, Baltimore through an access award to our late colleague Dr Richard Todd (Psychiatry, Washington University School of Medicine, St Louis). Statistical analyses were partly conducted at the Genetic Cluster Computer (http:// www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). SEM, SM and GWM are supported by the National Health and Medical Research Council Fellowship Scheme. NRW and DRN are supported by the Australian Research Council Future Fellowship Scheme. Funding Information: We would like to record our appreciation for much practical support from our late colleague Walter J Muir, Professor of Developmental Psychiatry at the University of Edinburgh and especially for his many stimulating ideas for genetic studies in depression. We thank Margaret Van Beck for sample collection and Lee Murphy, Wellcome Trust Clinical Research Facility, Western General Hospital, Crewe Road South, Edinburgh, for sample management. The collection of the Edinburgh cohort was supported by grants from The Wellcome Trust, London and the Chief Scientist Office of the Scottish Government. Funding Information: Additional funding was provided by National Institute of Mental Health Schizophrenia (NIMH) grant MH080403 to EJGCvdO and PFS. Control subjects from the NIMH Genetics Initiative, data and biomaterials are being collected by the {\textquoteleft}Molecular Genetics of Schizophrenia II{\textquoteright} collaboration. The investigators and coinvestigators are: ENH/Northwestern University, Evanston, IL, MH059571, Pablo V Gejman, MD (Collaboration Coordinator; PI), Alan R Sanders, MD; Emory University School of Medicine, Atlanta, GA, MH59587, Farooq Amin, MD (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN, BC, MSN (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879, C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA, MH59566, Raymond Crowe, MD (PI), Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert Freedman, MD (PI); University of Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson, MD (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School of Medicine, New York, NY, MH59586, Jeremy Silverman, PhD (PI).",
year = "2012",
month = jan,
doi = "10.1038/mp.2010.109",
language = "English",
volume = "17",
pages = "36--48",
journal = "Molecular Psychiatry",
issn = "1359-4184",
number = "1",
}