@article{75e08550c9bc46bca9b7b9dc7e782283,
title = "Evidence that duplications of 22q11.2 protect against schizophrenia",
abstract = "A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2 - the reciprocal of the well-known, risk-inducing deletion of this locus - are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.",
keywords = "22q11.2, CNV, duplication, protective, schizophrenia",
author = "E. Rees and G. Kirov and A. Sanders and Walters, {J. T.R.} and Chambert, {K. D.} and J. Shi and J. Szatkiewicz and C. O'Dushlaine and Richards, {A. L.} and Green, {E. K.} and I. Jones and G. Davies and Legge, {S. E.} and Moran, {J. L.} and C. Pato and M. Pato and G. Genovese and D. Levinson and J. Duan and W. Moy and G{\"o}ring, {H. H.H.} and D. Morris and P. Cormican and Kendler, {K. S.} and O'Neill, {F. A.} and B. Riley and M. Gill and A. Corvin and N. Craddock and P. Sklar and C. Hultman and Sullivan, {P. F.} and Gejman, {P. V.} and McCarroll, {S. A.} and O'Donovan, {M. C.} and Owen, {M. J.}",
note = "Funding Information: The 6882 schizophrenia cases from the discovery sample were genotyped at the Broad Institute and funded by a philanthropic gift to the Stanley Center for Psychiatric Research. We thank the participants and clinicians who took part in the Cardiff COGS study. This work was supported by a clinical research fellowship to JW from the MRC/Welsh Assembly Government and the Margaret Temple Award from the British Medical Association. We acknowledge Andrew Iles, David Parslow, Carissa Philipart and Sophie Canton for their work in recruitment, interviewing and rating. For the CLOZUK sample, we thank Novartis for their guidance and co-operation. We also thank staff at The Doctor{\textquoteright}s Laboratory, in particular Lisa Levett and Andrew Levett, for help and advice regarding sample acquisition. We acknowledge Kiran Mantripragada, Lesley Bates, Catherine Bresner and Lucinda Hopkins for laboratory sample management. The work at Cardiff University was funded by the Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418), the European Community{\textquoteright}s Seventh Framework Programme (HEALTH-F2–2010–241909 (Project EU-GEI) and a PhD to ER. Funding support for the Swedish study was provided by NIMH R01 MH077139 (P Sullivan), NIMH R01 MH095034 (P Sklar), the Stanley Center for Psychiatric Research, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, an ALF grant from Swedish County Council, the S{\"o}derstr{\"o}m K{\"o}nigska Foundation and the Netherlands Scientific Organization (NWO 645–000–003). For Irish/WTCCC2 study, funding was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). The LCL expression data was generated with grant support from RC2MH090030 and R01MH094091. The authors acknowledge the contribution of data from outside sources: (1) Genetic Architecture of Smoking and Smoking Cessation accessed through dbGAP: Study Accession: phs000404.v1.p1. Funding support for genotyping, which was performed at the Center for Inherited Disease Research (CIDR), was provided by 1 ⨯ 01 HG005274–01. CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (U01 HG004446). Funding support for collection of data sets and samples was provided by the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the University of Wisconsin Transdisciplinary Tobacco Use Research Center (P50 DA019706, P50 CA084724). (2) High Density SNP Association Analysis of Melanoma: Case-Control and Outcomes Investigation, dbGaP Study Accession: phs000187.v1.p1: Research support to collect data and develop an application to support this project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740 and 5R01CA133996. (3) Genetic Epidemiology of Refractive Error in the KORA (Kooperative Gesundheitsforschung in der Region Augsburg) Study, dbGaP Study Accession: phs000303.v1.p1. Principal Investigators: Dwight Stambolian, University of Pennsylvania, Philadelphia, PA, USA; H Erich Wichmann, Institut f{\"u}r Humangenetik, Helmholtz-Zentrum M{\"u}nchen, Germany, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.",
year = "2014",
month = jan,
doi = "10.1038/mp.2013.156",
language = "American English",
volume = "19",
pages = "37--40",
journal = "Molecular psychiatry",
issn = "1359-4184",
publisher = "Springer Nature",
number = "1",
}