Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2

M. C. O'Donovan, N. Norton, H. Williams, T. Peirce, V. Moskvina, I. Nikolov, M. Hamshere, L. Carroll, L. Georgieva, S. Dwyer, P. Holmans, J. L. Marchini, C. C.A. Spencer, B. Howie, H. T. Leung, I. Giegling, A. M. Hartmann, H. J. Möller, D. W. Morris, Y. ShiG. Feng, P. Hoffmann, P. Propping, C. Vasilescu, W. Maier, M. Rietschel, S. Zammit, J. Schumacher, E. M. Quinn, T. G. Schulze, N. Iwata, M. Ikeda, A. Darvasi, S. Shifman, L. He, J. Duan, A. R. Sanders, D. F. Levinson, R. Adolfsson, U. Ösby, L. Terenius, E. G. Jönsson, S. Cichon, M. M. Nöthen, M. Gill, A. P. Corvin, D. Rujescu, P. V. Gejman, G. Kirov, N. Craddock, N. M. Williams, M. J. Owen, P. V. Gejman, A. R. Sanders, J. Duan, D. F. Levinson, N. G. Buccola, B. J. Mowry, R. Freedman, F. Amin, D. W. Black, J. M. Silverman, W. J. Byerley, C. R. Cloninger

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Abstract

We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

Original languageAmerican English
Pages (from-to)30-36
Number of pages7
JournalMolecular Psychiatry
Volume14
Issue number1
DOIs
StatePublished - 25 Jan 2009

Bibliographical note

Funding Information:
This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The UK research was supported by grants from the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50 MH066392-05A1. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland), and the Wellcome Trust. We are grateful to Professor John Waddington for sample recruitment. Irish controls were supplied by Dr Joe McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the ‘Bundesminister-ium für Bildung und Forschung’ (BMBF), the Alfried Krupp von Bohlen und Halbach-Stiftung and in Bethesda the work was supported in part by the Intramural Program of the NIMH. 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, HUGR (www.hugr.org). In Sweden support was obtained from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3), the Wallenberg Foundation and the HUBIN project. The following authors are included under the Molecular Genetics of Schizophrenia Collaboration: PV Gejman, AR Sanders, J Duan (Evanston Healthcare and Northwestern University, IL, USA), DF Levinson (Stanford University, CA, USA), NG Buccola (Louisiana State University, LA, USA), BJ Mowry (University of Queensland, Brisbane, Australia), R Freedman (University of Colorado Health Science Centre, Denver, USA), F Amin (Emory University, Atlanta, USA), DW Black (University of Iowa College of Medicine, IA, USA), JM Silverman (Mount Sinai School of Medicine, New York, USA), WJ Byerley (University of California, San Francisco, USA), CR Cloninger (Washington University).

Keywords

  • FGFR2
  • Genome-wide association study
  • Schizophrenia

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