Evidence for a gene influencing blood pressure on chromosome 17 - Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study

Hypertension is a leading cause of morbidity and mortality. Efforts to iden tify hypertension genes have focused on 3 approaches: mendelian disorders, candidate genes, and genome-wide scans. Thus far, these efforts have not id entified genes that contribute substantively to overall blood pressure (BP) variation in the community. A 10-centiMorgan (cM) density genome-wide scan was performed in the largest families from 2 generations of Framingham Hea rt Study participants. Heritability and linkage for long-term mean systolic and diastolic BP phenotypes were analyzed by use of SOLAR software. Herita bility estimates were based on BP measurements in 1593 families. Genotyping was performed on 1702 subjects from 332 large families, and BP data were a vailable for 1585 (93%) genotyped subjects who contributed 12 588 longitudi nal BP observations. The mean age was 47 years, and mean BP was 127/80 (sys tolic/diastolic) mm Hg. Long-term systolic and diastolic BP phenotypes had high heritability estimates, 0.57 and 0.56, respectively. For systolic BP, multipoint log-of-the-odds (LOD) scores >2.0 were located on chromosome 17 at 67 cM (LOD 4.7, P=0.0000016) and 94 cM (LOD 2,2). For diastolic BP, LOD scores >2.0 were identified on chromosome 17 (74 cM, LOD 2.1) and chromosom e 18 (7 cM, LOD 2.1). Using a genome-wide scan, we found strong evidence fo r a BP quantitative trait locus on chromosome 17. Follow-up studies are war ranted to identify the gene or genes in this quantitative trait locus that influence BP. Such knowledge could extend our understanding of the genetic basis of essential hypertension and have implications for the evaluation an d treatment of patients with high BP.