Hypertension within the African American community

Introduction

Adoption, twin, and family studies document a significant heritable component to blood pressure levels and to hypertension. Family studies controlling for a common environment indicate that blood pressure heritability is in the range of 15% to 35%.1-3 In twin studies, heritability estimates of blood pressure are 60% for men and 30% to 40% for women.3-5 Nevertheless, genetic studies of hypertension in human populations remain challenging because of the likely multiplicity of contributing genes, the modest nature of gene effects, and the genetic heterogeneity among populations.

One fruitful approach to identifying genes of hypertension included studies in a limited number of families with early onset of hypertension and other characteristic phenotypes.6

However, the relevance of these genetic variants to hypertension in the general population remains to be determined.

Hypertension in African American Community

Association study approaches have included the study of candidate genes and genes identified from whole-genome linkage scans. Polymorphisms within a relatively large number of candidate genes have been tested for association with hypertension, and the results have been inconsistent.7

The development of thousands of microsatellite genetic markers has made whole-genome scans feasible. There are several recent reports of genome-wide scans in diverse populations attempting to link either blood pressure itself or a clinical diagnosis of hypertension to specific chromosomal loci.8-19 These studies have included sib pairs concordant for hypertension, as well as siblings who are extremely divergent for blood pressure. Although evidence for linkage of blood pressure with specific chromosomal regions has been observed in individual studies, results have not been consistent across studies. The lack of consistency among studies may reflect the fact that blood pressure is a difficult phenotype to assess because of its minute-to-minute variation and because of the potential confounding effects of antihypertensive medications. In addition, blood pressure is the culmination of interactions among autonomic, cardiovascular, renal, and endocrine control systems. Each of these systems may be influenced by different genes and different environments.

Our long-term goal is to focus on the physiological pathways that determine arterial pressure. In an effort to link hypertension-related phenotypes with specific chromosomal loci, total-genome scans were performed in African American sib pairs concordant for hypertension. Studies were performed in African Americans because of the high prevalence of hypertension and hypertension-related cardiovascular disease in this ethnic group.20 The purpose of this report is to describe the results of the linkage analyses of outpatient phenotypes obtained in the affected sib pairs.

Lander and Kruglyak25 published criteria for the significance of a LOD score in genome scans. However, these calculations were based on assumptions not explicitly found in most studies (eg, infinitely dense map of markers), and they do not take into account the intrinsic properties of a particular data set. One robust method, which aims to provide realistic assessment of significance by incorporating the actual marker density used in a study, the marker informativeness, and the pedigree structure for the data set with regard to each phenotype, uses simulation and permutation procedures.26 Using these approaches, we generated "simulated" data sets by randomly permutating ...