Linkage relationships between a major gene for catechol-o-methyltransferase activity and 25 polymorphic marker systems.

Segregation analysis has provided evidence suggesting the existence of a major gene for catechol-o-methyltransferase (COMT) activity in man. Five large families (4 Caucasian, 1 black), with a total of 1,189 individuals, were ascertained as part of a genetic study of blood pressure. Erythrocyte COMT activity and status at 25 polymorphic genetic marker loci were determined on more than 518 individuals in these pedigrees. Genetic linkage analysis of COMT with each of the 25 marker loci was performed in two ways: 1) using parameter estimates from segregation analysis of untransformed COMT activity, and 2) using parameter estimates from segregation analysis of the power transformation of the COMT activity that maximized the likelihood of the genetic hypothesis in each family. Tight and close linkage were excluded at 21 and 15 loci, respectively. A lod score of 1.27 at theta = 0.1 was found between the loci for COMT activity and phosphogluconate dehydrogenase (PGD). Transformation of the data had little effect on the outcome of the linkage analysis.