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Identification of loci associated with schizophrenia by genome-wide association and follow-up

Abstract

We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10−5 in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 × 10−4), and the overall pattern of replication was unlikely to occur by chance (P = 9 × 10−8). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 × 10−7) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 × 10−9).

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Acknowledgements

The UK research was supported by grants from the MRC and the Wellcome Trust. We are grateful to the Wellcome Trust Case Control Consortium for access to control genotypes (and to the individuals acknowledged in that respect in ref. 4) and their contribution to the genome-wide study, and to the Welsh e-Science Centre at Cardiff University for access to computing resources for some of this work. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland) and the Wellcome Trust. We are grateful to J. Waddington for sample recruitment. Irish controls were supplied by J. McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the 'Bundesministerium für Bildung und Forschung' (BMBF) and the Alfried Krupp von Bohlen und Halbach-Stiftung. We also thank the Department of Psychiatry, LMU Munich for clinical characterization of the Munich subjects and the processing of the samples. Recruitment in Munich was partially supported by GlaxoSmithKline. The Ashkenazi samples are part of the Hebrew University Genetic Resource.

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M.C.O'D., M.J.O., and N.C. directed this study and the collection of the UK sample. M.C.O'D. and M.J.O. took primary responsibility for drafting the manuscript assisted by N.N. and H.W. Collaborative scientific direction, replication sample collections, diagnoses and construction of case-control material were led by A.C., M.G., and D.W.M. (Ireland), D.R. (Munich, Germany), W.M., M.R., M.M.N., S.C., J.S. and P.P. (Bonn, Germany), G.K. (Bulgaria), L.H. and G.F. (China); N.I. (Japan) and S.S. and A.D. (Israel). J.L.M., C.C.A.S. and H.-T.L. were responsible for procedures related to calling Affymetrix genotypes. Replication genotyping was performed and analyzed by N.N., H.W., T.P., L.C., L.G. and S.D. (Cardiff); C.V. and P.Hoffmann (Bonn); Y.S. (China); S.S. (Israel); and M.I. (Japan). I.N. developed the database for the GWA project in which the data were stored, the primary analyses were performed and the results visualized. V.M. and P.Holmans supervised the association statistics to which N.N. additionally contributed. M.H. and N.C. were responsible for most of the quality control procedures. Additional scientific coordination of clinical sample collection and diagnosis was performed by S.Z., E.M.Q., A.M.H., H.-J.M., I.G. and T.G.S. All authors discussed the results and approved the manuscript.

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Correspondence to Michael C O'Donovan or Michael J Owen.

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Supplementary Figures 1–3, Supplementary Tables 1–3, Supplementary Methods, Supplementary Note (PDF 1097 kb)

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O'Donovan, M., Craddock, N., Norton, N. et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 40, 1053–1055 (2008). https://doi.org/10.1038/ng.201

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