Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia

Shinsaku Arai, Hiroki Shibata, Mayumi Sakai, Hideaki Ninomiya, Nakao Lwata, Norio Ozaki, Yasuyuki Fukumaki

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Objective As dysfunction of glutamatergic neurotransmission is one of the plausible hypotheses for the pathogenesis of schizophrenia, genes involved in the glutamate neurotransmitter system are candidates for schizophrenia susceptibility. The aim of this study is to clarify the contribution of two genes encoding glutamate metabolic enzymes: the glutamic acid decarboxylase 2 gene (GAD2) and the glutamine synthetase gene (GLUL), in schizophrenia. Methods We genotyped 300 Japanese schizophrenia patients and 300 healthy controls for 14 single nucleotide polymorphisms (SNPs) in GAD2 (approximately 91 kb in size) and six SNPs in GLUL (approximately 14 kb in size). We examined 'single-point' association as well as pairwise haplotype association for all SNPs with schizophrenia. Results We observed no significant 'single-point' associations with the disease in any of the 20 SNPs after correction for multiple testing using False Discovery Rate. We also observed no significant haplotype associations with False Discovery Rate. Furthermore, we analyzed gene-gene interactions, including six glutamate receptor genes we have reported previously in the association studies of GRIA4, GRIN2D, GRIK3, GRIK4, GRIK5, and GRM3, using the multifactor dimensionality reduction method. The best interaction model, however, did not show the statistical significance. Conclusion These results suggest that GAD2 and GLUL do not play a major role in schizophrenia pathogenesis and there is no gene-gene interaction between the eight genes in the Japanese population. Psychiatr Genet 19:6-13

元の言語英語
ページ(範囲)6-13
ページ数8
ジャーナルPsychiatric Genetics
19
発行部数1
DOI
出版物ステータス出版済み - 2 1 2009

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Glutamate Decarboxylase
Schizophrenia
Genes
Single Nucleotide Polymorphism
Haplotypes
glutamine synthetase 2
Glutamic Acid
Multifactor Dimensionality Reduction
Viverridae
Glutamate Receptors
Synaptic Transmission
Neurotransmitter Agents

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry

これを引用

Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. / Arai, Shinsaku; Shibata, Hiroki; Sakai, Mayumi; Ninomiya, Hideaki; Lwata, Nakao; Ozaki, Norio; Fukumaki, Yasuyuki.

:: Psychiatric Genetics, 巻 19, 番号 1, 01.02.2009, p. 6-13.

研究成果: ジャーナルへの寄稿記事

Arai, Shinsaku ; Shibata, Hiroki ; Sakai, Mayumi ; Ninomiya, Hideaki ; Lwata, Nakao ; Ozaki, Norio ; Fukumaki, Yasuyuki. / Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. :: Psychiatric Genetics. 2009 ; 巻 19, 番号 1. pp. 6-13.
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abstract = "Objective As dysfunction of glutamatergic neurotransmission is one of the plausible hypotheses for the pathogenesis of schizophrenia, genes involved in the glutamate neurotransmitter system are candidates for schizophrenia susceptibility. The aim of this study is to clarify the contribution of two genes encoding glutamate metabolic enzymes: the glutamic acid decarboxylase 2 gene (GAD2) and the glutamine synthetase gene (GLUL), in schizophrenia. Methods We genotyped 300 Japanese schizophrenia patients and 300 healthy controls for 14 single nucleotide polymorphisms (SNPs) in GAD2 (approximately 91 kb in size) and six SNPs in GLUL (approximately 14 kb in size). We examined 'single-point' association as well as pairwise haplotype association for all SNPs with schizophrenia. Results We observed no significant 'single-point' associations with the disease in any of the 20 SNPs after correction for multiple testing using False Discovery Rate. We also observed no significant haplotype associations with False Discovery Rate. Furthermore, we analyzed gene-gene interactions, including six glutamate receptor genes we have reported previously in the association studies of GRIA4, GRIN2D, GRIK3, GRIK4, GRIK5, and GRM3, using the multifactor dimensionality reduction method. The best interaction model, however, did not show the statistical significance. Conclusion These results suggest that GAD2 and GLUL do not play a major role in schizophrenia pathogenesis and there is no gene-gene interaction between the eight genes in the Japanese population. Psychiatr Genet 19:6-13",
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