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

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.

• Authors: 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 Shi, G 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 Osby, 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, Molecular Genetics of Schizophrenia Collaboration
• Journal: Molecular psychiatry (Mol Psychiatry) Vol. 14 Issue 1 Pg. 30-6 (Jan 2009) ISSN: 1476-5578 [Electronic] England
• PMID: 18813210 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Adult
• Aged
• Aged, 80 and over
• Chromosomes, Human, Pair 10
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genome-Wide Association Study (methods)
• Genotype
• Humans
• Linkage Disequilibrium
• Male
• Meta-Analysis as Topic
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)
• Schizophrenia (genetics)
• Young Adult