From a combined base population of over 20,000 screened probands, a sample of 1,200 sibships have been indexed with 2 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 studied 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. Epidemiologic 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 of absence seem to help determine the likelihood of expressing specific genetic predispositions to hypertension.
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