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Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia.

Abstract
Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population.
AuthorsHiroki Shibata, Ayako Tani, Tomoyuki Chikuhara, Rumiko Kikuta, Mayumi Sakai, Hideaki Ninomiya, Nobutada Tashiro, Nakao Iwata, Norio Ozaki, Yasuyuki Fukumaki
JournalPsychiatry research (Psychiatry Res) Vol. 167 Issue 1-2 Pg. 88-96 (May 15 2009) ISSN: 0165-1781 [Print] Ireland
PMID19351574 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptors, Glutamate
  • Receptors, Metabotropic Glutamate
Topics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes (genetics)
  • Humans
  • Linkage Disequilibrium (genetics)
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide (genetics)
  • Receptors, Glutamate (genetics)
  • Receptors, Metabotropic Glutamate (genetics)
  • Schizophrenia (genetics)

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