Further evidence of transmission disequilibrium of the catechol-O-methyl transferase (COMT) gene in schizophrenia in a Chinese population

Abstract

Several lines of evidence pointed to a locus for psychosis near the COMT gene on chromosome 22q11. We previously reported linkage disequilibrium between Chinese schizophrenic subjects and a Val158Met polymorphism in exon 4 of the COMT gene [Li et al., 1996]. We have now genotyped an additional four biallelic polymorphic markers (promoter/Hind III, exon 3/Pml I, exon 4/Bcl I, and exon 6/Bgl I) in 200 family trios, consisting of Han Chinese schizophrenic subjects and their parents. These five polymorphic markers (including of Val158Met) were in strong linkage disequilibrium with each other (P value from 0.0001 to 0) except between exon 4/Bcl I and exon6/Bgl I (P = 0.77). The data were analysed using the transmission disequilibrium test (TDT) for individual polymorphism markers and haplotypes between paired markers. We found evidence of linkage disequilibrium for one polymorphism alone in exon 3/Pml I (P = 0.02, two tailed), but others were not significant. When we used haplotype of pairs of markers for TDT analysis (ETDT2 program, David Curtis and Pak Sham), the results gave much stronger evidence of linkage disequilibrium between the COMT gene and schizophrenia. Seven haplotypes out of ten analysed and gave P value less than 0.05 (from 0.0006 to 0.036 for allele-wise). P values were 0.0006 for allele-wise and 0.004 for genotype-wise when using haplotype of Val158Met and exon 6/Bgl I for TDT analysis. Our results support the hypothesis that COMT is a susceptibility gene, or this region of chromosome 22 contains a susceptibility gene which is in linkage disequilibrium with the COMT gene.