Munafo MR, Bowes L, Clark TG, Flint J. Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry 10: 765-770

Cancer Research UK GPRG, Department of Clinical Pharmacology, University of Oxford, Oxford, UK.
Molecular Psychiatry (Impact Factor: 14.5). 09/2005; 10(8):765-70. DOI: 10.1038/
Source: PubMed


There is strong evidence for a genetic contribution to schizophrenia, but the contribution of individual candidate genes remains uncertain. We attempted to replicate a recent meta-analysis that reported an association of the catechol O-methyltransferase (COMT) Val allele with schizophrenia, and suggested that this effect may be moderated by ancestry. We included reports published subsequent to the original meta-analysis, and included a formal test of the moderating effect of ancestry in order to test whether the association operates differently in populations of European ancestry compared to populations of Asian ancestry. A corrected P-value for the 5% significance threshold was employed where appropriate, using Bonferroni's method, and studies that demonstrated departure from Hardy-Weinberg equilibrium among controls were excluded. When all studies were included in a meta-regression, there was evidence for a significant association of COMT Val allele frequency with schizophrenia case status and a significant main effect of ancestry. The interaction of COMT Val allele frequency and ancestry was also significant. However, when only studies that reported allele frequencies that did not depart significantly from Hardy-Weinberg equilibrium among controls were included, these effects were no longer significant. The results of our meta-analysis do not support an association between the COMT Val allele and schizophrenia case status, and do not support recent claims that this association may be moderated by ancestry.

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Available from: Taane G Clark, Jul 21, 2014
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    • "Thus, COMT is an excellent candidate gene for modulating dopamine levels and function in the cortex and for determining where on the inverted-U shaped curve of dopamine function an individual lies (Tunbridge et al. 2006). However, inconsistent behavioral data and performance meta-analyses support only a weak association between COMT polymorphisms and individual differences in PFC function (Barnett et al. 2007; Munafo et al. 2005). Nevertheless, investigations of individual differences with intermediate brain-based phenotypes, more sensitive for detecting gene effects on the brain (Green et al. 2008; Parasuraman & Jiang 2012), have found greater cortical processing efficiency in Met158 homozygotes compared to Val158 homozygotes, with heterozygotes displaying intermediate activation levels (Egan et al. 2001; Heinz & Smolka 2006). "
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    ABSTRACT: Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol-O-methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting state electroencephalographic (EEG) oscillations. In a sample of 62 healthy nonsmoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double-blind, placebo controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in fronto-central regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2015 · Genes Brain and Behavior
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    • "The association between schizophrenia and the high activity Val allele has been analysed in several studies that have culminated in different meta-analysis which showed inconsistent results [11] [12]. The influence of sex on the involvement of COMT genotype in schizophrenia vulnerability has been reported in several studies [13] [14] [15] [16]. "
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    ABSTRACT: Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
    Full-text · Article · Feb 2015 · BioMed Research International
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    • "The pooled OR in the meta-analysis was calculated by weighting the individual ORs using the inverse of their variance [34]. The significance of the pooled OR was determined using a Z-test [37]. To test the reliability of the results, we also performed a sensitivity analysis after deleting any one of the included studies. "
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    ABSTRACT: Background Men who have sex with men (MSM) are a high risk population for human immunodeficiency virus (HIV) infection. Our study aims to find whether MSM who were recruited online had a higher prevalence of self-reported unprotected anal intercourse (UAI) than those who were recruited offline. Methods A meta-analysis was conducted from the results of published studies. The analysis was stratified by the participants’ geographic location, the sample size and the date of the last reported UAI. Results Based on fourteen studies, MSM who were recruited online (online-based group) reported that 33.9% (5,961/17,580) of them had UAI versus 24.9% (2,700/10,853) of MSM who were recruited offline (offline-based group). The results showed that it is more likely for an online-based MSM group to have UAI with male partners than an offline-based MSM group [odds ratio (OR) = 1.35, 95% CI = 1.13-1.62, P < 0.01]. The subgroup analysis results also showed that the prevalence of UAI was higher in the European subsample (OR = 1.38, 95% CI = 1.17-1.63, P < 0.01) and in sample sizes of more than 500 individuals (OR = 1.32, 95% CI = 1.09-1.61, P < 0.01) in the online group compared to the offline group. The prevalence of UAI was also significantly higher when the time of the last UAI was during the last 3 or more months (OR = 1.40, 95% CI = 1.13-1.74, P < 0.05) in the online group compared to the offline group. A sensitivity analysis was used to test the reliability of the results, and it reported that the results remained unchanged and had the same estimates after deleting any one of the included studies. Conclusions A substantial percentage of MSM were recruited online, and they were more inclined to engage in UAI than MSM who were recruited offline. Targeted interventions of HIV prevention programs or services are recommended when designing preventive interventions to be delivered via the Internet.
    Full-text · Article · May 2014 · BMC Public Health
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