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

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

doi:10.1016/j.schres.2009.02.019

Cited by 114 publications

(87 citation statements)

References 66 publications

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“…On the other hand, a study conducted in the Japanese population reported that the significant association between this SNP and schizophrenia could not be found, for example, 10.2% in patients versus 8.2% in control subjects, 27 and 8.7% in patients versus 8.6% in control subjects. 28 It is hard to expound on the discrepancies among the results of the studies at this stage. However, if the relative risk was small and/or MAF was low, the possibility of a type II error as a result of insufficient statistical power might be possible.…”

Section: Discussionmentioning

confidence: 99%

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality

et al. 2009

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Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using v 2 analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (P corr ¼ 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

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Section: Discussionmentioning

confidence: 99%

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality

et al. 2009

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“…The association of rs4680 with psychosis phenotypes in the context of cannabis use has been difficult to replicate (Okochi et al., 2009; Zammit, Owen, Evans, Heron, & Lewis, 2011; Zammit et al., 2007). This may be due to heterogeneity between studies, including differences in age of assessment of psychotic symptoms and variability in the allelic frequency of rs4680 between different ethnic groups including apparently similar ethnic groups with differing degrees of admixture.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use

et al. 2017

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Objective COMT rs4680 (Val158Met) genotype moderates the effect of cannabis on the age of onset of psychosis (AoP). We investigated the association between rs4680 and AoP, after adjusting for relevant covariates, in a Canadian Caucasian sample.MethodsOne hundred and sixty‐nine subjects with psychosis were recruited. AoP, defined as age of DSM‐IV diagnosis was established using the Structured Clinical Interview for DSM‐IV. Cannabis use data were collected using a self‐report computerized questionnaire. DNA was extracted from saliva and genotyping of the COMT Val158Met polymorphism was done by SNaPshot and TaqMan assays. Logistic regression and Kaplan–Meier analysis results are reported.ResultsIn those who had used cannabis before 20 years of age, rs4680 had a trend level effect on AoP (median AoP: Val/Val < Val/Met < Met/Met 19.37, 20.95, 21.24 years, respectively; log‐rank test p = .051).ConclusionOur data are indicative of the need to further investigate the association between the COMT rs4680 variant and AoP in the context of adolescent cannabis use.

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“…This single-nucleotide polymorphism (SNP) has been widely studied for its connection with SZ susceptibility, but with conflicting results. Meta-analyses do not support the association with SZ (Fan et al, 2005;Munafo et al, 2005;Okochi et al, 2009). Several previous studies in the Han Chinese population failed to find a positive association with SZ (Fan et al, 2005;Yu et al, 2007;Kang et al, 2010;Chen et al, 2011); but these studies chiefly focused on only one SNP and the sample sizes involved were relatively small.…”

Section: Introductionmentioning

confidence: 82%

No Association of Catechol-O-Methyltransferase Polymorphisms with Schizophrenia in the Han Chinese Population

Zhang

Liu

Chen

et al. 2012

Genetic Testing and Molecular Biomarkers

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Aims: Genetics play a major role in the etiology of schizophrenia (SZ). Catechol-O-methyltransferase (COMT) is one of the promising candidate genes for SZ. A nonsynonymous single-nucleotide polymorphism (SNP), rs4680, causing a Valine (Val) to Methionine (Met) substitution, has been widely studied in relation to psychiatric phenotypes, including SZ, but with conflicting results. We conducted a two-stage study to examine the association of COMT polymorphisms with SZ in the Han Chinese population. Results: Association analysis of nine SNPs in 768 patients and 1348 controls failed to detect any positive markers or haplotypes. Then, we tested rs4680 in a validation sample of 963 patients and 992 controls, and no significant association was observed, but the cases significantly deviated from Hardy-Weinberg equilibrium ( p = 5.7e-4). There was no association of rs4680 with SZ in the combined sample (n = 4071, p = 0.110, odds ratio = 1.08). Conclusions: Our results do not support the association of COMT with SZ in the Han Chinese population.

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

Cited by 114 publications

References 66 publications

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality

Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use

No Association of Catechol-O-Methyltransferase Polymorphisms with Schizophrenia in the Han Chinese Population

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