Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure - The Framingham Heart Study

Background - Arterial stiffness and mean arterial pressure variably contribute to systolic hypertension and increased cardiovascular risk. However, few prior community-based studies have evaluated the genetics of arterial stiffness and separate mean and pulsatile components of blood pressure. Methods and Results - Using arterial tonometry, we evaluated heritability and linkage of forward and reflected wave amplitude, mean arterial pressure, and carotid-femoral pulse wave velocity (CFPWV) in 1480 participants representing 817 pedigrees in the Framingham Study offspring cohort. In 204 families with tonometry data, a genome-wide scan was performed with microsatellite markers that covered the genome at 10-cM intervals. Heritability estimates were moderate for reflected wave amplitude ( h(2) = 0.48), forward wave amplitude (h(2) = 0.21), CFPWV (h(2) = 0.40), and mean arterial pressure (h(2) = 0.33). Variance components linkage analysis identified 2 regions of linkage for reflected wave amplitude: chromosome 4 at 181 cM ( logarithm of odds [LOD] = 4.93, permuted P = 0.002) and chromosome 8 at 33 cM (LOD = 3.27, permuted P = 0.058). There was 1 region of linkage for forward wave amplitude on chromosome 7 at 174 cM (LOD = 2.88, permuted P = 0.017). There were several regions of suggestive linkage for CFPWV: chromosome 2 at 94 cM (LOD = 2.46), chromosome 7 at 29 cM (LOD = 2.50), chromosome 13 at 108 cm (LOD = 2.10), and chromosome 15 at 108 cM (LOD = 2.48). There was 1 region of suggestive linkage for mean arterial pressure on chromosome 1 at 192 cM ( LOD = 2.18). Conclusions - Arterial stiffness measures and mean and pulsatile components of blood pressure are heritable and appear to have genetic determinants that may be linked to separate genetic loci in humans.