GENETIC DETERMINANTS OF HGH BLOOD PRESSURE STUDY

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We have established a group of experienced investigators dedicated to localizing, identifying, and evaluating common polymorphic variation in genes involved in determining interindividual differences in blood pressure (BP) levels and essential hypertension (EHYT) status in three racial groups: African-Americans, Mexican-Americans, and Non-Hispanic Whites. Each collaborating investigator is responsible for an essential element of our Network: Boerwinkle (genotyping and linkage analyses), Ferrell (genotyping), Hanis (recruiting Mexican-Americans), Hutchinson (recruiting African-Americans), Sing (cladistic and prediction analyses and data management), and Turner (recruiting Non-Hispanic Whites and measuring physiologic variables). Our Network proposes to carry out five specific aims to localize and characterize the genetic determinants of high BP. Aim 1 will use robust sibling pair linkage methods in 500 hypertensive sibling pairs in each racial group (a total of 1,500 sibling pairs) to localize genes influencing interindividual differences in the occurrence of EHYT. Aims 2 and 3 will take advantage of previously collected BP and intermediate predictor trait data from 1,488 normotensive sibling pairs from the Rochester Family Heart Study to localize genes contributing to EHYT. The proposed linkage analyses (Aims 1-3) will use both an extensive array of candidate genes and a large number of anonymous markers throughout the genome. Aim 4 will use multiple diallelic sequence polymorphisms and cladistic analyses within a linked gene to identify haplotypes for further DNA sequencing in order to identify candidate functional DNA sequence variation contributing to interindividual differences in BP levels and EHYT status. Aim 5 will evaluate the ability of candidate functional DNA sequence variation to predict EHYT status in the three racial groups.