Evidence for a gene influencing heart rate on chromosome 4 among hypertensives

While mechanisms are poorly understood, resting heart rate has been shown to be a strong predictor of the risk of cardiovascular disease, cancer, and all-cause mortality. We performed a genome scan for quantitative trait loci influencing the resting heart rate among 962 Caucasians and 1,124 African-Americans in the Hypertension Genetic Epidemiology Network (HyperGEN), a multi-center study of genetic and environmental factors related to hypertension. The NHLBI Mammalian Genotyping Service typed a total of 391 anonymous microsatellite markers, spaced roughly equally throughout the genome. Within each race and sex, heart rate was adjusted for covariates, including age, age(2), study center, body mass index, beta-blocker use, alcohol consumption, smoking, number of city blocks walked per day, and number of hours watching television. Genome scans were performed using variance component linkage analysis as implemented by GENEHUNTER (version 2) for each race, using race-specific marker allele frequencies derived from random samples. The highest lod score detected in Caucasians was 2.14 on chromosome 4 (at 195.06 cM); a lod score of 1.14 was found at the same locus among the African-Americans, and a lod score of 3.18 resulted when the two racial groups were combined. Evidence was also found on chromosome 10 to support a recent report of an association between heart rate and the beta1 adrenergic receptor. The suggestive evidence for linkage found on chromosome 4 in both Caucasian and African-American hypertensive sib pairs indicates that further investigation on that region may be warranted to locate a gene influencing variability in resting heart rate.