Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients

Masashi Ikeda, Nakao Iwata, Tatsuyo Suzuki, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Toshiya Inada, Hiroshi Ujike, Norio Ozaki

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Abstract

Background: Several investigations suggest that abnormalities in γ-amino butyric acid (GABA) neurotransmission systems may be related to the pathophysiology of schizophrenia. A GABAA receptor gene cluster on 5q31-35 (β2 [GABRB2], α6 [GABRA6], α1 [GABRA1], and γ2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility. Methods: We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects). Results: In the first-set scan, we found a significant association of two htSNPs in GABRA1, but no association of GABRB2, GABRA6, and GABRG2. In the following second-set analysis, however, we could not confirm these significant associations. Conclusions: These results indicate that this gene cluster may not play a major role in Japanese schizophrenia. They also raised an alert with regard to preliminary genetic association analysis using a small sample size.

Original languageEnglish
Pages (from-to)440-445
Number of pages6
JournalBiological Psychiatry
Volume58
Issue number6
DOIs
Publication statusPublished - 15-09-2005

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Chromosomes, Human, Pair 5
GABA-A Receptors
Schizophrenia
Multigene Family
Single Nucleotide Polymorphism
Butyric Acid
Linkage Disequilibrium
Synaptic Transmission
Sample Size
gamma-Aminobutyric Acid
Haplotypes
Genes

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Ikeda, Masashi ; Iwata, Nakao ; Suzuki, Tatsuyo ; Kitajima, Tsuyoshi ; Yamanouchi, Yoshio ; Kinoshita, Yoko ; Inada, Toshiya ; Ujike, Hiroshi ; Ozaki, Norio. / Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients. In: Biological Psychiatry. 2005 ; Vol. 58, No. 6. pp. 440-445.
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Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients. / Ikeda, Masashi; Iwata, Nakao; Suzuki, Tatsuyo; Kitajima, Tsuyoshi; Yamanouchi, Yoshio; Kinoshita, Yoko; Inada, Toshiya; Ujike, Hiroshi; Ozaki, Norio.

In: Biological Psychiatry, Vol. 58, No. 6, 15.09.2005, p. 440-445.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Suzuki, Tatsuyo

AU - Kitajima, Tsuyoshi

AU - Yamanouchi, Yoshio

AU - Kinoshita, Yoko

AU - Inada, Toshiya

AU - Ujike, Hiroshi

AU - Ozaki, Norio

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N2 - Background: Several investigations suggest that abnormalities in γ-amino butyric acid (GABA) neurotransmission systems may be related to the pathophysiology of schizophrenia. A GABAA receptor gene cluster on 5q31-35 (β2 [GABRB2], α6 [GABRA6], α1 [GABRA1], and γ2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility. Methods: We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects). Results: In the first-set scan, we found a significant association of two htSNPs in GABRA1, but no association of GABRB2, GABRA6, and GABRG2. In the following second-set analysis, however, we could not confirm these significant associations. Conclusions: These results indicate that this gene cluster may not play a major role in Japanese schizophrenia. They also raised an alert with regard to preliminary genetic association analysis using a small sample size.

AB - Background: Several investigations suggest that abnormalities in γ-amino butyric acid (GABA) neurotransmission systems may be related to the pathophysiology of schizophrenia. A GABAA receptor gene cluster on 5q31-35 (β2 [GABRB2], α6 [GABRA6], α1 [GABRA1], and γ2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility. Methods: We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects). Results: In the first-set scan, we found a significant association of two htSNPs in GABRA1, but no association of GABRB2, GABRA6, and GABRG2. In the following second-set analysis, however, we could not confirm these significant associations. Conclusions: These results indicate that this gene cluster may not play a major role in Japanese schizophrenia. They also raised an alert with regard to preliminary genetic association analysis using a small sample size.

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