Association between homozygosity at the COMT gene locus and obsessive compulsive disorder

A functional polymorphism in the coding region of the catechol O-methyltransferase (COMT) gene has been reported in previous studies to be associated with obsessive compulsive disorder (OCD), particularly in males [Karayiorgou et al., 1997, 1999]. Using a family-based population analysis, we attempted to replicate these findings in a group of 72 OCD patient/parent trios collected from Buffalo, New York, and Toronto, Canada. Analysis of allele and genotype frequencies using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) did not identify an association between a particular allele and OCD as had been previously reported. Furthermore, no evidence was found to support the findings of a gender-based association for COMT when the patients and the parents of the same gender were compared. However, our genotype results (n = 72) demonstrate a tendency for association between homozygosity at the COMT locus and OCD (homozygosity analysis: chi(2) = 5.66, P = 0.017; genotypic analysis: chi(2) = 5.78, P = 0.056). Although these findings do not replicate the previous reports, they do provide limited support to demonstrate a trend for homozygosity at the COMT locus in the OCD patients and, in turn, further implicate a potential role for COMT in the genetic etiology of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:721-724, 2000.