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

Mol Psychiatry. 2009 Jan;14(1):30-6. doi: 10.1038/mp.2008.108. Epub 2008 Sep 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Receptor, Fibroblast Growth Factor, Type 2