Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2.
O'Donovan MC., Norton N., Williams H., Peirce T., Moskvina V., Nikolov I., Hamshere M., Carroll L., Georgieva L., Dwyer S., Holmans P., Marchini JL., Spencer CCA., Howie B., Leung H-T., Giegling I., Hartmann AM., Möller H-J., Morris DW., Shi Y., Feng G., Hoffmann P., Propping P., Vasilescu C., Maier W., Rietschel M., Zammit S., Schumacher J., Quinn EM., Schulze TG., Iwata N., Ikeda M., Darvasi A., Shifman S., He L., Duan J., Sanders AR., Levinson DF., Adolfsson R., Osby U., Terenius L., Jönsson EG., Cichon S., Nöthen MM., Gill M., Corvin AP., Rujescu D., Gejman PV., Kirov G., Craddock N., Williams NM., Owen MJ., Molecular Genetics of Schizophrenia Collaboration None.
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.