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

Journal article

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.

Authors: O'Donovan, M; Norton, N; Williams, H; Peirce, T; Moskvina, V

• Publication status: Published
• Journal: Molecular psychiatry
• Volume: 14
• Issue: 1
• Pages: 30-36
• Publication date: 2009-01-01
• DOI: 10.1038/mp.2008.108
• EISSN: 1476-5578
• ISSN: 1359-4184
• Language: English
• Keywords: Polymorphism, Single Nucleotide; Genome-Wide Association Study; Linkage Disequilibrium; Receptor, Fibroblast Growth Factor, Type 2; Molecular Genetics of Schizophrenia Collaboration; Aged; Humans; Young Adult; Chromosomes, Human, Pair 10; Schizophrenia; Middle Aged; Genotype; Meta-Analysis as Topic; Genetic Predisposition to Disease; Aged, 80 and over; Adult; Gene Frequency; Female; Male