Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia

Linkage disequilibrium mapping using SNPs evenly distributed across the gene region

Chieko Makino, Yo Fujii, Rumiko Kikuta, Naotsugu Hirata, Ayako Tani, Atsushi Shibata, Hideaki Ninomiya, Nobutada Tashiro, Hiroki Shibata, Yasuyuki Fukumaki

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Abstract

The glutamatergic dysfunction hypothesis suggests that genes involved in the glutamate neurotransmitter system are candidates for schizophrenia-susceptibility genes. We have been conducting systematic studies of the association between glutamate receptors and schizophrenia. We report on a positive association of some haplotypes of the AMPA receptor subunit GluR4 gene (GRIA4) with schizophrenia. We genotyped 100 Japanese schizophrenics and 100 controls for six single nucleotide polymorphism (SNP) markers distributed at intervals of about 50 kb in the GRIA4 region, and estimated the degree of linkage disequilibrium (LD) between the SNPs. We constructed haplotypes of the SNPs in LD using the EM algorithm to test their association with schizophrenia. Significant associations were detected for the combination of SNP4-5 (x 2 = 12.54, df = 3, P = 0.0057, P = 0.029 with Bonferroni correction) and for the combination of SNP3-4-5 (x2 = 18.9, df = 7, P = 0.0085, P = 0.043 with Bonferroni correction). These results suggest that at least one susceptibility locus for schizophrenia is located within or very close to the GRIA4 region in Japanese.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume116 B
Issue number1
Publication statusPublished - Jan 1 2003

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Chromosome Mapping
Linkage Disequilibrium
Haplotypes
Single Nucleotide Polymorphism
Schizophrenia
Genes
Glutamate Receptors
Neurotransmitter Agents
Glutamic Acid
AMPA 4 glutamate receptor ionotropic

All Science Journal Classification (ASJC) codes

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

Cite this

Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia : Linkage disequilibrium mapping using SNPs evenly distributed across the gene region. / Makino, Chieko; Fujii, Yo; Kikuta, Rumiko; Hirata, Naotsugu; Tani, Ayako; Shibata, Atsushi; Ninomiya, Hideaki; Tashiro, Nobutada; Shibata, Hiroki; Fukumaki, Yasuyuki.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 116 B, No. 1, 01.01.2003, p. 17-22.

Research output: Contribution to journalArticle

Makino, Chieko ; Fujii, Yo ; Kikuta, Rumiko ; Hirata, Naotsugu ; Tani, Ayako ; Shibata, Atsushi ; Ninomiya, Hideaki ; Tashiro, Nobutada ; Shibata, Hiroki ; Fukumaki, Yasuyuki. / Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia : Linkage disequilibrium mapping using SNPs evenly distributed across the gene region. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2003 ; Vol. 116 B, No. 1. pp. 17-22.
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