Studies of left ventricular (LV) hypertrophy detected by echocardiography demonstrate its importance in cardiovascular morbidity and mortality, independent of blood pressure and other cardiovascular risk factors. The goal of this project is to evaluate the genetic determinants of LV hypertrophy. Building upon HyperGEN (a network established to investigate the genetic determinants of hypertension as part of the NHLBI Genetic Determinants of High Blood Pressure RFA (#6-94-011), this application proposes to perform a targeted echocardiographic examination on 2,575 HyperGEN participants in four field centers as part of the HyperGEN clinical examination. The HyperGEN study is designed to identify the genetic determinants of hypertension by selecting severely and mildly affected hypertensives from existing epidemiologic populations, affected siblings of these probands, a random sample of individuals from the cohorts, and normotensive relatives of the probands. These individuals will be examined over a three year period, beginning in August, 1996. There are five specific aims for this echocardiography project. First, the investigators will characterize LV structure and function in 2,575 individuals. Second, they will define LV structural phenotypes based on four geometric patterns(normal geometry, concentric remodeling, concentric LV hypertrophy, and eccentric LV hypertrophy). Third, they will examine a highly select group of candidate genes and their association with LV mass (measured as a quantitative trait to increase statistical power) and geometric patterns. Fourth, using quantitative trait loci analyses, the investigators will test for linkage of 240 anonymous, evenly spaced genetic markers with LV mass and geometric patterns. The fifth aim is to evaluate interactions between genes and potential risk factors for LV hypertrophy (insulin, glucose, blood pressure response to mental and physical stressors, dietary and urinary electrolytes, obesity) and LV mass and geometry. The proposed project has the advantages of (i) incorporation into an already funded study designed to examine. the genetic determinants of hypertension (more than 500,000 individual genotypes are measured as part of HyperGEN); (ii) recruitment of participants from on-going population-based studies of well-characterized cohorts; (iii) collaboration with experienced investigators in research echocardiography, an experienced echocardiography reading center (under the direction of Dr. Richard Devereux), statistical expertise in association and linkage analyses (directed by Dr. D. C. Rao), and genetic testing by a state-of-the-art laboratory(directed by Dr. Lalouel). It will, therefore, be an important and cost-effective contribution to the knowledge and understanding about the genetics of LV hypertrophy.
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