@article{31f7108cc008479ca34745dc32933875,
title = "A mega-analysis of genome-wide association studies for major depressive disorder",
abstract = "Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10−8), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083–53 822 102, minimum P=5.9 × 10−9 at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.",
keywords = "genetics, genome-wide association study, major depressive disorder, mega-analysis, meta-analysis, CARDIOVASCULAR RISK-FACTORS, NATIONAL COMORBIDITY SURVEY, SEROTONIN TRANSPORTER GENE, BIPOLAR DISORDER, SUSCEPTIBILITY LOCI, PSYCHIATRIC-DISORDERS, MENTAL-DISORDERS, MOOD DISORDERS, TWIN REGISTRY, HUMAN HEIGHT",
author = "{Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium} and Stephan Ripke and Wray, {Naomi R} and Lewis, {Cathryn M} and Hamilton, {Steven P} and Weissman, {Myrna M} and Gerome Breen and Byrne, {Enda M} and Blackwood, {Douglas H R} and Boomsma, {Dorret I} and Sven Cichon and Heath, {Andrew C} and Florian Holsboer and Susanne Lucae and Madden, {Pamela A F} and Martin, {Nicholas G} and Peter McGuffin and Pierandrea Muglia and Noethen, {Markus M} and Penninx, {Brenda P} and Pergadia, {Michele L} and Potash, {James B} and Marcella Rietschel and Danyu Lin and Bertram M{\"u}ller-Myhsok and Jianxin Shi and Stacy Steinberg and Grabe, {Hans J} and Paul Lichtenstein and Patrik Magnusson and Perlis, {Roy H} and Martin Preisig and Smoller, {Jordan W} and Kari Stefansson and Rudolf Uher and Zoltan Kutalik and Tansey, {Katherine E} and Alexander Teumer and Alexander Viktorin and Barnes, {Michael R} and Thomas Bettecken and Binder, {Elisabeth B} and Ren{\'e} Breuer and Castro, {Victor M} and Churchill, {Susanne E} and Coryell, {William H} and Nick Craddock and Craig, {Ian W} and Darina Czamara and MacIntyre, {Donald J} and Andrew McIntosh",
year = "2013",
month = apr,
doi = "10.1038/mp.2012.21",
language = "English",
volume = "18",
pages = "497--511",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "4",
}