@article{40733942cf994b6ea2f3e12f420e9ef8,
title = "Genome-wide association analysis of copy number variation in recurrent depressive disorder",
abstract = "Large, rare copy number variants (CNVs) have been implicated in a variety of psychiatric disorders, but the role of CNVs in recurrent depression is unclear. We performed a genome-wide analysis of large, rare CNVs in 3106 cases of recurrent depression, 459 controls screened for lifetime-absence of psychiatric disorder and 5619 unscreened controls from phase 2 of the Wellcome Trust Case Control Consortium (WTCCC2). We compared the frequency of cases with CNVs against the frequency observed in each control group, analysing CNVs over the whole genome, genic, intergenic, intronic and exonic regions. We found that deletion CNVs were associated with recurrent depression, whereas duplications were not. The effect was significant when comparing cases with WTCCC2 controls (P=7.7 × 10 -6, odds ratio (OR) =1.25 (95% confidence interval (CI) 1.13-1.37)) and to screened controls (P=5.6 × 10 -4, OR=1.52 (95% CI 1.20-1.93). Further analysis showed that CNVs deleting protein coding regions were largely responsible for the association. Within an analysis of regions previously implicated in schizophrenia, we found an overall enrichment of CNVs in our cases when compared with screened controls (P=0.019). We observe an ordered increase of samples with deletion CNVs, with the lowest proportion seen in screened controls, the next highest in unscreened controls and the highest in cases. This may suggest that the absence of deletion CNVs, especially in genes, is associated with resilience to recurrent depression.",
keywords = "CNVs, GWAS, depression",
author = "Rucker, {J. J.H.} and G. Breen and D. Pinto and I. Pedroso and Lewis, {C. M.} and S. Cohen-Woods and R. Uher and A. Schosser and M. Rivera and Aitchison, {K. J.} and N. Craddock and Owen, {M. J.} and L. Jones and I. Jones and A. Korszun and P. Muglia and Barnes, {M. R.} and M. Preisig and O. Mors and M. Gill and W. Maier and J. Rice and M. Rietschel and F. Holsboer and Farmer, {A. E.} and Craig, {I. W.} and Scherer, {S. W.} and P. Mcguffin",
note = "Funding Information: This study was funded by a joint grant from the UK Medical Research Council and GlaxoSmithKline (G0701420). James Rucker was supported by a fellowship from the Wellcome Trust (086635). Alexandra Schosser was supported by the Erwin-Schroedinger Fellowship (J2647) of the Austrian Science Funds. Alexandra Schosser, Inti Pedroso and Sarah Cohen-Woods received financial support from the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King{\textquoteright}s College London. Margarita Rivera was supported by a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme. The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428 and GlaxoSmithKline contributed by funding an add-on project in the London centre. The population-based study in Lausanne was supported by three grants from the Swiss National Science Foundation (No. 3200B0-105993, No. 3200B0-118308, No. 33CSCO-122661) and from GlaxoSmithKline (Psychiatry Center of Excellence for Drug Discovery and Genetics Division, Drug Discovery Verona, R&D). Rudolf Uher and Peter McGuffin are supported by a grant from the European Commission (Grant Agreement No. 115008). Geno-typing was performed at the Centre Nationale De Genotypage, Evry, Paris, with acknowledgement to Simon Heath, Ivo Gut and Mark Lathrop. We acknowledge the contribution of phase 2 of the Wellcome Trust Case Control Consortium in providing access to control data sets from the 1958 British birth cohort and the national blood service cohort.",
year = "2013",
month = feb,
doi = "10.1038/mp.2011.144",
language = "English",
volume = "18",
pages = "183--189",
journal = "Molecular Psychiatry",
issn = "1359-4184",
number = "2",
}