Genome-wide scan for pulse pressure in the National Heart, Lung and Blood Institute's Framingham Heart Study

The objective of this study was to assess heritability and identify chromosomal regions showing evidence of linkage to pulse pressure ( PP), a simple indicator of proximal conduit vessel stiffness. Blood pressure data were analyzed for 8478 members of the National Heart, Lung and Blood Institute's (NHLBI) Framingham Heart Study. Long-term PP was defined using 2-stage analysis. First, the difference between systolic and diastolic blood pressure was averaged over all qualifying clinic examinations. In the second stage, mean PP was adjusted for mean age, time period of examination, and body mass index by regression analysis. PP values were available for 6421 individuals in 1593 families for heritability estimation and for 2492 individuals in 330 families for linkage analysis. Microsatellite markers covering the genome at 10 cM intervals were typed by the NHLBI Mammalian Genotyping Service; genome scan data were available on 1585 individuals with PP data. Heritability estimates of long-term PP accounting for hypertension treatment and for ignoring treatment were 0.52 and 0.51, respectively. Variance component linkage analysis identified several locations with suggestive evidence of linkage: chromosome 15 at 122 cM ( logarithm of odds [LOD] = 2.94), chromosome 7 at 71 cM (LOD = 2.42), chromosome 5 at 53 cM (LOD = 2.03), and chromosome 10 at 81 cM (LOD = 1.83) for PP accounting for treatment. LOD scores were slightly lower when ignoring treatment, with the exception of a peak on chromosome 10 at 81 cM (LOD = 2.58). In conclusion, we have demonstrated a substantial genetic component to PP and have identified 4 chromosomal regions that may harbor genes influencing vascular stiffness.