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

O'Donovan, Michael Conlon ORCID:, Norton, Nadine ORCID:, Williams, Hywel John ORCID:, Peirce, Timothy Rowan, Escott-Price, Valentina ORCID:, Nikolov, Ivan, Hamshere, Marian Lindsay ORCID:, Carroll, Liam Stuart, Georgieva, Lyudmila, Dwyer, Sarah Lynne, Holmans, Peter Alan ORCID:, Marchini, J. L., Spencer, C. C. A., Howie, B., Leung, H.T., Giegling, I., Hartmann, A. M., Möller, H.J., Morris, D. W., Shi, Y., Feng, G., Hoffmann, P., Propping, P., Vasilescu, C., Maier, W., Rietschel, M., Zammit, Stanley ORCID:, Schumacher, J., Quinn, E. M., Schulze, T. G., Iwata, N., Ikeda, M., Darvasi, A., Shifman, S., He, L., Duan, J., Sanders, A. R., Levinson, D. F., Adolfsson, R., Ösby, U., Terenius, L, Jönsson, E. G., Cichon, S., Nöthen, M. M., Gill, M., Corvin, A. P., Rujescu, D., Gejman, P. V., Kirov, George ORCID:, Craddock, Nicholas John ORCID:, Williams, Nigel Melville ORCID: and Owen, Michael John ORCID: 2009. Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. Molecular Psychiatry 14 (1) , pp. 30-36. 10.1038/mp.2008.108

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: FGFR2; schizophrenia; genome-wide association study FGFR2; schizophrenia; genome-wide association study
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 06 Nov 2022 13:42

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