High blood pressure, or hypertension, affects nearly one in three adults and is the most common risk factor for coronary heart disease, stroke, and end-stage renal disease. It is a primary or contributing cause of death in over 11 % of the total number of deaths, and accounted for an estimated $66.4 billion in healthcare costs in 2007. Blood pressure rises steadily throughout life. Therefore, discovering the molecular factors that underlie blood pressure ontogeny may be fundamental to understanding hypertension. The proposed research represents a collaborative effort to use existing specimens, high-quality phenotypic data on cardiovascular disease risk factors, and state-of-the-art analytical methods to identify and replicate genetic effects influencing longitudinal cardiovascular disease (CVD) risk factors profiles, with a special emphasis on blood pressure, and to characterize their interactions with relevant environmental factors, specifically body weight profiles, physical fitness, psychosocial influences, and dietary intake. These goals are fundamental to developing new approaches to detection, treatment, and prevention of high blood pressure and its associated CVD consequences. The primary setting is that of the Coronary Artery Risk Development in Young Adults (CARDIA), a prospective, multi-center investigation of the natural history and etiology of cardiovascular disease in 5,115 African-Americans and Whites 18-30 years old at the time of initial examination. We propose to conduct whole genome association analyses on 1,930 African-American and 2,064 white CARDIA participants with available DNA to identify an assumed 15-20 genes associated with inter-individual variation in blood pressure profiles during the critical transition period from young adulthood to early middle-age. Replication of results will be facilitated through collaborations with the Atherosclerosis Risk In Communities (ARIC) study, the Rochester Family Heart Study (RFHS), and the Bogalusa Heart Study (BHS). The CARDIA cohort provides a unique opportunity to examine the context-dependent effects of genetic variation influencing CVD risk factors profiles, by virtue of the extensive data on lifestyle, behavior, and physiologic risk factors collected from young adulthood to early middle-age, a period when the development and progression of CVD accelerates, but when few clinically recognized events have occurred, minimizing confounding effects of drugs associated with treatment of such events, or potential bias due to CVD-related death of the participants.
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