Meta-analysis of association between genetic variants in COMT and schizophrenia

An update

Tomo Okochi, Masashi Ikeda, Taro Kishi, Kunihiro Kawashima, Yoko Kinoshita, Tsuyoshi Kitajima, Yoshio Yamanouchi, Makoto Tomita, Toshiya Inada, Norio Ozaki, Nakao Iwata

Research output: Contribution to journalArticle

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Abstract

A common functional polymorphism, Val108/158Met (rs4680), and haplotypes rs737865-rs4680-rs165599 in the Catechol-O-methyltransferase gene (COMT) have been extensively examined for association to schizophrenia; however, results of replication studies have been inconsistent. The aim of this study was to comprehensively evaluate the genetic risk of COMT for schizophrenia. First, we performed a mutation scan to detect the existence of potent functional variants in the 5′-flanking and exon regions. Second, we conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) in COMT [19 SNPs including six possible functional SNPs (rs2075507, rs737865, rs4680, rs165599, rs165849)] and schizophrenia in large Japanese samples (schizophrenics 1118, controls 1100). Lastly, we carried out a meta-analysis of 5 functional SNPs and haplotypes (rs737865-rs4680-rs165599). No novel functional variant was detected in the mutation scan. There is no association between these tagging SNPs in COMT and Japanese schizophrenia. In this updated meta-analysis, no evidence was found for an association between Val108/158Met polymorphisms, rs6267, rs165599, and haplotypes (rs7378655-rs4680-rs165599) and schizophrenia, although rs2075507 and rs737865 showed trends for significance in allele-wise analyses (P = 0.039 in a multiplicative model, P = 0.025 in a recessive model for rs2075507, P = 0.018 in a dominant model for rs737865, uncorrected). This significance did not remain, however, after correcting the P-values using a false discovery rate controlling procedure. Our results suggest that the COMT is unlikely to contribute to susceptibility to schizophrenia.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalSchizophrenia Research
Volume110
Issue number1-3
DOIs
Publication statusPublished - 01-05-2009

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Catechol O-Methyltransferase
Meta-Analysis
Schizophrenia
Single Nucleotide Polymorphism
Haplotypes
Genes
Mutation
5' Flanking Region
Case-Control Studies
Exons
Alleles

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Okochi, Tomo ; Ikeda, Masashi ; Kishi, Taro ; Kawashima, Kunihiro ; Kinoshita, Yoko ; Kitajima, Tsuyoshi ; Yamanouchi, Yoshio ; Tomita, Makoto ; Inada, Toshiya ; Ozaki, Norio ; Iwata, Nakao. / Meta-analysis of association between genetic variants in COMT and schizophrenia : An update. In: Schizophrenia Research. 2009 ; Vol. 110, No. 1-3. pp. 140-148.
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Okochi, T, Ikeda, M, Kishi, T, Kawashima, K, Kinoshita, Y, Kitajima, T, Yamanouchi, Y, Tomita, M, Inada, T, Ozaki, N & Iwata, N 2009, 'Meta-analysis of association between genetic variants in COMT and schizophrenia: An update', Schizophrenia Research, vol. 110, no. 1-3, pp. 140-148. https://doi.org/10.1016/j.schres.2009.02.019

Meta-analysis of association between genetic variants in COMT and schizophrenia : An update. / Okochi, Tomo; Ikeda, Masashi; Kishi, Taro; Kawashima, Kunihiro; Kinoshita, Yoko; Kitajima, Tsuyoshi; Yamanouchi, Yoshio; Tomita, Makoto; Inada, Toshiya; Ozaki, Norio; Iwata, Nakao.

In: Schizophrenia Research, Vol. 110, No. 1-3, 01.05.2009, p. 140-148.

Research output: Contribution to journalArticle

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T1 - Meta-analysis of association between genetic variants in COMT and schizophrenia

T2 - An update

AU - Okochi, Tomo

AU - Ikeda, Masashi

AU - Kishi, Taro

AU - Kawashima, Kunihiro

AU - Kinoshita, Yoko

AU - Kitajima, Tsuyoshi

AU - Yamanouchi, Yoshio

AU - Tomita, Makoto

AU - Inada, Toshiya

AU - Ozaki, Norio

AU - Iwata, Nakao

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N2 - A common functional polymorphism, Val108/158Met (rs4680), and haplotypes rs737865-rs4680-rs165599 in the Catechol-O-methyltransferase gene (COMT) have been extensively examined for association to schizophrenia; however, results of replication studies have been inconsistent. The aim of this study was to comprehensively evaluate the genetic risk of COMT for schizophrenia. First, we performed a mutation scan to detect the existence of potent functional variants in the 5′-flanking and exon regions. Second, we conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) in COMT [19 SNPs including six possible functional SNPs (rs2075507, rs737865, rs4680, rs165599, rs165849)] and schizophrenia in large Japanese samples (schizophrenics 1118, controls 1100). Lastly, we carried out a meta-analysis of 5 functional SNPs and haplotypes (rs737865-rs4680-rs165599). No novel functional variant was detected in the mutation scan. There is no association between these tagging SNPs in COMT and Japanese schizophrenia. In this updated meta-analysis, no evidence was found for an association between Val108/158Met polymorphisms, rs6267, rs165599, and haplotypes (rs7378655-rs4680-rs165599) and schizophrenia, although rs2075507 and rs737865 showed trends for significance in allele-wise analyses (P = 0.039 in a multiplicative model, P = 0.025 in a recessive model for rs2075507, P = 0.018 in a dominant model for rs737865, uncorrected). This significance did not remain, however, after correcting the P-values using a false discovery rate controlling procedure. Our results suggest that the COMT is unlikely to contribute to susceptibility to schizophrenia.

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