Admixture Mapping for Hypertension in African Americans

Howard University, Washington DC

Investigators

Linked publications & trials

Abstract

The goal of this project is to contribute to our understanding of the genetic basis of hypertension (HTN) in[unreadable] African-Americans (AA). Hypertension disproportionately affects AA and its complications contribute[unreadable] immensely to health disparity experienced by AA through increased morbidity and mortality from stroke,[unreadable] heart failure, kidney failure and coronary heart disease. It is now accepted that HTN results from a complex[unreadable] interplay between genetic and environmental factors. However, the environmental risk factors, which include[unreadable] lifestyle, dietary and psycho-social factors, have been better characterized than the genetic ones. Linkage[unreadable] and candidate gene studies have so far provided limited success across studies and population groups.[unreadable] Building on the success of a previously funded study of the genetic epidemiology of AA families in the[unreadable] Washington DC metropolitan area, we propose to enroll a population sample of HTN cases and unaffected[unreadable] controls, genotype a panel of ancestry informative markers (AIM) in the sample and utilize the admixture[unreadable] mapping approach to identify genomic regions associated with HTN. During a clinical examination, we will[unreadable] collect demographic information and measure blood pressure, anthropometry and body composition. Blood[unreadable] will be drawn for biochemical assays (sodium, potassium, creatinine, urea, glucose) and several other[unreadable] molecular phenotypes (including cortisol, endothelin-1, C-reactive protein, insulin, leptin). Genomic DNA will[unreadable] be extracted. A published panel of 3,011 well-characterized AIM single nucleotide polymorphisms (SNPs)[unreadable] will be genotyped in 500 HTN cases and 500 controls. Locus-genome statistics (for cases only) and casecontrol[unreadable] statistics will be calculated and used to identify ancestral genomic regions that have susceptibility[unreadable] genes for HTN. The identified regions will be followed up with a SNP fine map at a density of approximately 10 kb to[unreadable] further refine the regions and move closer to the genes that need further study by resequencing, mutation[unreadable] detection, replication and functional studies. Taking advantage of the unique historic experience of AA and a[unreadable] new genetic strategy (admixture mapping), this project has the potential to provide useful insights into how[unreadable] genetic inheritance predisposes to hypertension and to contribute to our understanding of how to develop[unreadable] better strategies for hypertension prevention, treatment and control.[unreadable]