Abstract #302217

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JSM 2003 Abstract #302217
Activity Number: 219
Type: Contributed
Date/Time: Tuesday, August 5, 2003 : 9:00 AM to 10:50 AM
Sponsor: ENAR
Abstract - #302217
Title: Commingling Analysis of Dopamine-Beta-Hydroxylase: A Second Locus?
Author(s): Sarah G. Buxbaum*+ and Cyrus Zabetian and Robert C. Elston and Joseph Cubells
Companies: University of Pittsburgh and University of Washington and Metro Health Medical Center and Yale University
Address: A300 Crabtree Hall, Pittsburgh, PA, 15213-2535,
Keywords: commingling ; DBH ; multiple regression ; genetic ; SNP
Abstract:

We have analyzed a quantitative trait, the activity level of dopamine-beta-hydroxylase in blood plasma, and showed that a polymorphism in the 5' flanking region of the DBH gene accounts for 35% (n=58), 51% (n=376), and 52% (n=53), respectively, of the variation in samples from African American, Caucasian, and Japanese populations. In doing so, we determined that a square root function was the best transformation of the trait and that an additive Mendelian model fit the data best. Eleven additional SNPs were genotyped in the DBH locus and 340 subjects in the Caucasian sample had nonmissing data at these 12 SNPs. Using this sample, a multiple regression of these SNPs was consistent with C1021T, or a tightly linked locus, being the causative polymorphism. A commingling analysis of the trait, adjusted for the C1021T genotype, was performed. The difference in the -2ln likelihoods between a model allowing one mean, and a model allowing two means approached significance (p=.06); adjusting for both C1021T and a proximal 3' SNP showed a significant difference (p=.01). The results suggest a second locus, not in the DBH gene, contributes to the variance of dopamine-beta-hydroxylase activity.

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