Association of the catechol-O-methyltransferase val158met polymorphism and anxiety-related traits: a meta-analysis

Objectives The aims of this study were (i) to examine genotypic association of the catechol-O-methyltransferase (COMT) val158met polymorphism with anxiety-related traits with a meta-analysis; (ii) to examine sex and ethnicity as moderators of the association; and (iii) to evaluate whether the association differed by particular anxiety traits. Methods Association studies of the COMT val158met polymorphism and anxiety traits were identified from the PubMed or PsycInfo databases, conference abstracts, and listserv postings. Exclusion criteria were (a) pediatric samples, (b) exclusively clinical samples, and (c) samples selected for a nonanxiety phenotype. Standardized mean differences in anxiety between genotypes were aggregated to produce mean effect sizes across all available samples, and for subgroups stratified by sex and ethnicity (Whites vs. Asians). Construct-specific analysis was conducted to evaluate the association of COMT with neuroticism, harm avoidance, and behavioral inhibition. Results Twenty-seven eligible studies (N=15 979) with available data were identified. Overall findings indicate sex-specific and ethnic-specific effects: valine homozygotes had higher neuroticism than methionine homozygotes in studies of White males [mean effect size=0.13; 95% CI 0.02, 0.25; P=0.03], and higher harm avoidance in studies of Asian males (=0.43; 95% CI 0.14, 0.72; P=0.004). No significant associations were found in women and effect sizes were diminished when studies were aggregated across ethnicity or anxiety traits. Conclusion This meta-analysis provides evidence for sex and ethnic differences in the association of the COMT val158met polymorphism with anxiety traits. Our findings contribute to current knowledge on the relation between prefrontal dopaminergic transmission and anxiety.