Genome-wide linkage analysis of pulse pressure in Mexican Americans

Pulse pressure, a measure of aortic stiffness, is a strong predictor of car diovascular mortality. To locate genes that affect pulse pressure, we perfo rmed genetic analysis on randomly ascertained families in the San Antonio F amily Heart Study. Pulse pressure was defined as the difference between sys tolic and diastolic blood pressures. Likelihood methods were used to constr uct a model that had both single-locus and polygenic components for 46 fami lies (1308 individuals). The single-locus component included sex-specific a nd genotype-specific effects of both age and body mass index. Using this mo del, we then performed 2-point Linkage analysis in 10 families (440 individ uals) that were among the largest of the 46 families and that had been geno typed for 399 polymorphic markers. The model that contained only the polyge nic component and simple effects of the covariates showed pulse pressure he ritability of 0.21. When the single-locus component was added, the sex-spec ific and genotype-specific effects of age and body mass index were highly s ignificant (P<0.002). The full model accounted for 73% of the total variati on of pulse pressure. Linkage analysis using this model with each marker re vealed 4 markers with lod scores >1.9, which is the Lander-Kruglyak suggest ive linkage standard. D21S1440 had a lod score of 2.78 with a recombination fraction (theta) of 0.02, D7S1799 had a lod score of 2.04 (theta =0.01), D 8S1100 had a lod score of 1.98 (theta =0.08), and D18S844 had a lod score o f 1.95 (theta =0.11). These results are highly correlated with results invo lving systolic blood pressure, indicating that pulse pressure may not be ge netically distinct from systolic blood pressure.