A genetic epidemiology network of 9 centers, including Boston University/Framingham, will study genetic and interacting non-genetic determinants of hypertension. Previously collected data on hypertension and family history in white subjects from the Framingham Study and the Family Heart Study, and in black subjects at other sites, allow the identification of a large and equal sample of black and non-black families with 2+ hypertensive siblings, untreated relatives and controls (total 4,600 subjects) for genetic association and sibship linkage studies (to test 20 candidate genes and anonymous markers totalling about 750,000 genotype determinations); as well as a rich battery of epidemiologic analyses assessing family history and genotype information in combination with important non-genetic factors. The data coordinating center, four field centers (including Framingham), and biochemistry lab center of the Family Heart Study (""""""""FHS"""""""") plus two additional black field centers and DNA lab center form this network. The investigators in this network have published major findings regarding the genetics and epidemiology of hypertension and state-of-the-art technology in molecular biology, biochemistry, epidemiology, and specialized statistics for genetic epidemiology. These investigators have a proven track record of productive collaboration between institutions. The study design in this proposal takes full advantage of strong collaboration both within this network and between this and other networks operating under the same cooperative agreement. From a combined base population of over 20,000 screened probands, a sample of l,200 sibships have been indexed with two or more siblings having hypertension diagnosed before age 60. These sibships have been chosen to be equally divided into subgroups by race (black and non-black) and severity of hypertension (severe and mild) and can be further stratified by other pertinent factors (body mass index, plasma lipids, age of onset of hypertension, etc.). The choice of methods (genetic association and model-free sibship linkage) and large sample size with ability to analyze within more homogeneous subgroups provide good power to detect specific genetic loci promoting hypertension despite considerable heterogeneity. Replication studies in independent populations (these subjects versus previously studies Utah sibships and versus other collaborative Networks) will allow the confirmation of genetic loci for genes promoting hypertension. Loci found by other networks will also be rapidly tested in our subjects for confirmation. Epidemiological analyses of persons with and without one or more confirmed genes for hypertension in combination with non-genetic factors and intermediate phenotypes will identify gene- environment interactions and specific lifestyle factors whose presence or absence seem to help determine the likelihood of expressing specific genetic predispositions to hypertension.
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