Genome-Wide Linkage Analysis of Pulse Pressure in Mexican Americans

Abstract

Pulse pressure, a measure of aortic stiffness, is a strong predictor of cardiovascular mortality. To locate genes that affect pulse pressure, we performed genetic analysis on randomly ascertained families in the San Antonio Family Heart Study. Pulse pressure was defined as the difference between systolic and diastolic blood pressures. Likelihood methods were used to construct a model that had both single-locus and polygenic components for 46 families (1308 individuals). The single-locus component included sex-specific and genotype-specific effects of both age and body mass index. Using this model, we then performed 2-point linkage analysis in 10 families (440 individuals) that were among the largest of the 46 families and that had been genotyped for 399 polymorphic markers. The model that contained only the polygenic component and simple effects of the covariates showed pulse pressure heritability of 0.21. When the single-locus component was added, the sex-specific and genotype-specific effects of age and body mass index were highly significant (P <0.002). The full model accounted for 73% of the total variation of pulse pressure. Linkage analysis using this model with each marker revealed 4 markers with lod scores >1.9, which is the Lander-Kruglyak suggestive linkage standard. D21S1440 had a lod score of 2.78 with a recombination fraction (θ) of 0.02. D7S1799 had a lod score of 2.04 (θ=0.01), D8S1100 had a lod score of 1.98 (θ=0.08), and D18S844 had a lod score of 1.95 (θ=0.11). These results are highly correlated with results involving systolic blood pressure, indicating that pulse pressure may not be genetically distinct from systolic blood pressure.