Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia

Hiromi Takaki, Rumiko Kikuta, Hiroki Shibata, Hideaki Ninomiya, Nobutada Tashiro, Yasuyuki Fukumaki

研究成果: ジャーナルへの寄稿記事

42 引用 (Scopus)

抄録

The glutamatergic dysfunction has been implicated in pathophysiology of schizophrenia. The Group III metabotropic glutamate receptor 4 (mGluR4), 6, 7, and 8 are thought to modulate glutamatergic transmission in the brain by inhibiting glutamate release at the synapse. We tested association of schizophrenia with GRM8 using 22 single nucleotide polymorphisms (SNPs) with the average intervals of 40.3 kb in the GRM8 region in 100 case-control pairs for the SNPs. Although we observed significant associations of schizophrenia with two SNPs, SNP18 (rs2237748, allele: P = 0.0279; genotype: P = 0.0124) and SNP19 (rs2299472, allele: P = 0.0302; genotype: P = 0.0127), none of two SNPs showed significant association with disease after Bonferroni correction. Both SNP18 and SNP19 were included in a large region (>330 kb) in which SNPs are in linkage disequilibrium (LD) at the 3′ region of GRM8. We also tested haplotype association of schizophrenia with constructed haplotypes of the SNPs in LD. Significant associations were detected for the combinations of SNP5-SNP6 (ξ2 = 18.12, df = 3, P = 0.0004, P corr = 0.0924 with Bonferroni correction), SNP4-SNP5-SNP6 (ξ2 = 27.50, df = 7, P = 0.0075, P corr = 0.015 with Bonferroni correction), and SNP5-SNP6-SNP7 (ξ2 = 23.92, df = 7, P = 0.0011, P corr = 0.0022 with Bonferroni correction). Thus, we conclude that at least one susceptibility locus for schizophrenia is located within the GRM8 region in Japanese.

元の言語英語
ページ(範囲)6-14
ページ数9
ジャーナルAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
128 B
発行部数1
出版物ステータス出版済み - 7 1 2004

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Single Nucleotide Polymorphism
Schizophrenia
Genes
Linkage Disequilibrium
Haplotypes
Alleles
Genotype
Synapses
metabotropic glutamate receptor 8
Glutamic Acid
Brain

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

これを引用

Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia. / Takaki, Hiromi; Kikuta, Rumiko; Shibata, Hiroki; Ninomiya, Hideaki; Tashiro, Nobutada; Fukumaki, Yasuyuki.

:: American Journal of Medical Genetics - Neuropsychiatric Genetics, 巻 128 B, 番号 1, 01.07.2004, p. 6-14.

研究成果: ジャーナルへの寄稿記事

Takaki, Hiromi ; Kikuta, Rumiko ; Shibata, Hiroki ; Ninomiya, Hideaki ; Tashiro, Nobutada ; Fukumaki, Yasuyuki. / Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia. :: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2004 ; 巻 128 B, 番号 1. pp. 6-14.
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abstract = "The glutamatergic dysfunction has been implicated in pathophysiology of schizophrenia. The Group III metabotropic glutamate receptor 4 (mGluR4), 6, 7, and 8 are thought to modulate glutamatergic transmission in the brain by inhibiting glutamate release at the synapse. We tested association of schizophrenia with GRM8 using 22 single nucleotide polymorphisms (SNPs) with the average intervals of 40.3 kb in the GRM8 region in 100 case-control pairs for the SNPs. Although we observed significant associations of schizophrenia with two SNPs, SNP18 (rs2237748, allele: P = 0.0279; genotype: P = 0.0124) and SNP19 (rs2299472, allele: P = 0.0302; genotype: P = 0.0127), none of two SNPs showed significant association with disease after Bonferroni correction. Both SNP18 and SNP19 were included in a large region (>330 kb) in which SNPs are in linkage disequilibrium (LD) at the 3′ region of GRM8. We also tested haplotype association of schizophrenia with constructed haplotypes of the SNPs in LD. Significant associations were detected for the combinations of SNP5-SNP6 (ξ2 = 18.12, df = 3, P = 0.0004, P corr = 0.0924 with Bonferroni correction), SNP4-SNP5-SNP6 (ξ2 = 27.50, df = 7, P = 0.0075, P corr = 0.015 with Bonferroni correction), and SNP5-SNP6-SNP7 (ξ2 = 23.92, df = 7, P = 0.0011, P corr = 0.0022 with Bonferroni correction). Thus, we conclude that at least one susceptibility locus for schizophrenia is located within the GRM8 region in Japanese.",
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