Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene val158/108Met polymorphism

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 = -.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 Val58/108Met 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.