Genome-Wide Multipoint Parametric Linkage Analysis of Pulse Pressure in Large, Extended Utah Pedigrees

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Abstract
High pulse pressure, a measure of arterial aging, is an important predictor of cardiovascular and general mortality. It has been suggested that the genetic etiology of pulse pressure is the same as systolic blood pressure. We performed a genome-wide, multipoint, parametric linkage analysis in 26 large, extended Utah pedigrees to locate genes affecting pulse pressure. Four parametric models were considered, including dominant and recessive modes of inheritance involving genes for high and low pulse pressure. Linkage analysis revealed 11 regions with a logarithm of the odds (LOD) >1.5, including 2 regions attaining genome-wide suggestive evidence for linkage after accounting for multiple tests. Inspecting pedigree-specific multipoint linkage evidence suggested that these 2 regions localized to 15.7 cM on chromosome 8p (LOD=2.89), between markers D8S136 and D8S1477, and 20.0 cM on chromosome 12q (LOD=2.59), between D12S1300 and D12S2070. Both regions were identified better by pulse pressure compared with equivalent analyses with systolic or diastolic blood pressure. Results for pulse pressure overlapped favorably with those of others for related blood pressure phenotypes and support the hypothesis that genes with pleiotropic effects on blood pressure phenotypes do exist, but that the genetic etiologies are not identical. In conclusion, our results suggest that pulse pressure might be of use for identifying genes involved in blood pressure phenotypes and arterial aging.