COMT (catechol-O-methyltransferase) encodes an enzyme that catalyzes the O-methylation and inactivation of catecholamine neurotransmitters, particularly dopamine, thereby regulating their biological half-lives. The enzyme also metabolizes catechol hormones and neuroactive drugs like L-DOPA [UniProt]. The most studied polymorphism is Val158Met (rs4680), which affects enzyme activity and subsequently dopamine levels in the brain 1. This polymorphism influences individual differences in self-consciousness and self-flexibility, with Val/Val genotypes (lower dopamine) showing higher private self-consciousness 1. COMT variants demonstrate ethnic-specific associations with disease susceptibility. In Asian populations, the Val158Met polymorphism shows significant association with Parkinson's disease risk, particularly in Japanese individuals 2, though meta-analyses suggest this is not a major risk determinant overall 3. For schizophrenia, the rs165599 polymorphism shows no general association, but sex-specific analysis reveals G allele carriers have increased risk in females 4. COMT variants also contribute to ethnic differences in pain sensitivity 5 and may influence antidepressive treatment response, particularly for electroconvulsive therapy 6. However, associations with tardive dyskinesia risk appear limited 7.