title: Replication study and meta-analysis of the genetic association of GRM3 gene polymorphisms with schizophrenia in a large Japanese case-control population.
abstract: The GRM3 gene, which encodes a metabotropic glutamate receptor, is an important candidate gene for susceptibility to schizophrenia. Two single nucleotide polymorphisms (SNPs), rs1468412 and rs2299225 in intron 3, were reported to be associated with schizophrenia in Japanese and Chinese populations, respectively. Haplotypes with these SNPs were also reported to be associated with schizophrenia. In the present study, we attempted to replicate these single marker and haplotype associations in a case-control study of 1,916 Japanese patients with schizophrenia and 1,915 Japanese control subjects. In addition to these two SNPs, we genotyped rs274622 in the promoter region of GRM3. In the present study, none of these polymorphisms were associated with schizophrenia (rs274622, allelic P = 0.68; rs1468412, allelic P = 0.74; rs2299225, allelic P = 0.20). Haplotypes constructed with these SNPs also were not associated with schizophrenia (P = 0.18-0.84). Meta-analysis of five case-control studies of more than 3,000 patients with schizophrenia and more than 3,000 control subjects did not support the associations of rs1468412 and rs2299225 with schizophrenia. Our data indicate that SNPs previously reported to be associated with schizophrenia do not contribute to genetic susceptibility to schizophrenia.
authors.affiliation: Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Talal
authors.initials: T
authors.lastname: Albalushi
authors.forename: Yasue
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D018094:Receptors, Metabotropic Glutamate