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Association of the Catechol-O-Methyltransferase (COMT)Val158Met Polymorphism and Anxiety-Related Traits: A Meta-AnalysisLewina O. Lee, Ph.D. 1,2 and Carol A. Prescott, Ph.D. 31 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts2 National Center for Posttraumatic Stress Disorder, Veterans Affairs Boston Healthcare System,Boston, Massachusetts3 Department of Psychology and Davis School of Gerontology, University of Southern California,Los Angeles, CaliforniaAbstractObjectives—The main goals of this study were: (i) to examine genotypic association of theCOMT val158met polymorphism with anxiety-related traits via a meta-analysis; (ii) to examinesex and ethnicity as moderators of the association, and (iii) to evaluate whether the associationdiffered by particular anxiety traits.Methods—Association studies of the COMT val18met polymorphism and anxiety traits wereidentified from the PubMed or PsycInfo databases, conference abstracts and listserv postings.Exclusion criteria were: (a) pediatric samples, (b) exclusively clinical samples, and (c) samplesselected for a non-anxiety phenotype. Standardized mean differences in anxiety betweengenotypes were aggregated to produce mean effect sizes across all available samples, and forsubgroups stratified by sex and ethnicity (Caucasians vs. Asians). Construct-specific analysis wasconducted to evaluate the association of COMT with neuroticism, harm avoidance, and behavioralinhibition.Results—Twenty seven eligible studies (N=15,979) with available data were identified. Overallfindings indicate sex-specific and ethnic-specific effects: Val homozygotes had higher neuroticismthan Met homozygotes in studies of Caucasian males ( , 95%CI: 0.02 – 0.25, p = 0.03),and higher harm avoidance in studies of Asian males ( , 95%CI: 0.14 – 0.72, p = 0.004).No significant associations were found in women and effect sizes were diminished when studieswere aggregated across ethnicity or anxiety traits.Conclusions: This meta-analysis provides evidence for sex and ethnicity differences in theassociation of the COMT val158met polymorphism with anxiety traits. Our findings contribute tocurrent knowledge on the relation between prefrontal dopaminergic transmission and anxiety.Correspondence to: Lewina O. Lee, Ph.D., 150 South Huntington Avenue (151-MAV), VA Boston Healthcare System, Boston, MA02130, lol@bu.edu, Phone:(857) 364-6364, Fax: (857) 364-4424.CONFLICT OF INTERESTThe authors declare no conflict of interest.NIH Public AccessAuthor ManuscriptPsychiatr Genet. Author manuscript; available in PMC 2015 April 01.Published in final edited form as:Psychiatr Genet. 2014 April ; 24(2): 52–69. doi:10.1097/YPG.0000000000000018.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript