Elsevier

Biological Psychiatry

Volume 64, Issue 2, 15 July 2008, Pages 137-144
Biological Psychiatry

Archival Report
Meta-Analysis of the Cognitive Effects of the Catechol-O-Methyltransferase Gene Val158/108Met Polymorphism

https://doi.org/10.1016/j.biopsych.2008.01.005Get rights and content

Background

Cognitive endophenotypes may further our understanding of the genetic basis of psychiatric disorders, and the catechol-O-methyltransferase (COMT) gene is a promising candidate gene for both cognitive function and disorder. We conducted a meta-analysis of reported associations between the COMT Val158/108Met polymorphism and measures of memory and executive function.

Methods

The PubMed database was searched for studies relating cognitive functions and the COMT Val158/108Met polymorphism. This enabled meta-analyses of six cognitive phenotypes (Trail Making task, verbal recall, verbal fluency, IQ score, n-back task, and Wisconsin Card Sorting Test). Data were extracted by two reviewers and included cognitive scores by COMT genotype, publication year, diagnostic status, ancestry, proportion of male participants, and whether genotype frequencies were consistent with Hardy-Weinberg equilibrium.

Results

We found no association between COMT genotype and the majority of phenotypes. There was evidence of association with IQ score (d = .06), which did not differ significantly by ancestry, sex, average sample age, or patient status. For the n-back task, there was no robust evidence for genetic association, but the effect size was significantly larger in patient (d = .40) than nonpatient (d = āˆ’.27) populations, larger in both samples with fewer male subjects, and those of greater average age. There was also evidence of publication bias and decreasing effect sizes with later publication.

Conclusions

Despite initially promising results, the COMT Val158/108Met polymorphism appears to have little if any association with cognitive function. Publication bias may hamper attempts to understand the genetic basis of psychological functions and psychiatric disorders.

Section snippets

Search Strategy and Inclusion Criteria

The PubMed database was searched to the end of August 2007 using combinations of the terms ā€œcatechol-O-methyltransferaseā€ or ā€œCOMTā€ and ā€œcognitive,ā€ ā€œcognition,ā€ ā€œIQ,ā€ ā€œintelligence,ā€ ā€œmemory,ā€ ā€œexecutive,ā€ ā€œWisconsin Card Sort*,ā€ and ā€œattention.ā€ Studies were excluded for the following reasons: no cognitive data reported, sample comprised patients with 22q11 deletion syndrome (who have only one copy of the COMT gene), groups matched by cognitive function, studies of a different COMT

Characteristics of Included Studies

The final dataset of 46 studies comprised 67 independent samples published between 2001 and 2007 where cognitive data was reported by COMT Val158/108Met genotype. These studies are described in Supplement 1.

Meta-analysis

Analyses were conducted separately for the following phenotypes: Trail Making task, verbal fluency, verbal recall, IQ score, n-back task accuracy, and Wisconsin Card Sorting Test perseverative errors.

Discussion

Meta-analyses showed no association between the COMT Val158/108Met variant and indices of memory or executive function, with the exception of a small association between genotype and n-back task performance in the opposite direction from that hypothesized, with evidence of significant between-study heterogeneity. When patient and nonpatient samples were considered separately, these effect sizes differed significantly, although in each case significant between-study heterogeneity remained. There

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