GWAS FOR CARDIOVASCULAR HEALTH IN ELDERLY PUERTO RICANS

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The rapid developments in genetic analyses have opened an exciting chapter in population health. There has been a tremendous rise in the reporting of genes and pol5Tnorphisms potentially impacting health outcomes. In particular, genome wide scanning technology and bioinformatics are providing exciting information on disease risk. However, most available data, and particularly genome-wide association (GWAS) studies, are based on non-Hispanic white populations. With the projected increase ofthe US Hispanic population and the rise of health disparities in this population, their inclusipn in genetic studies is imperative. We provide a unique resource, in that we have a cohort of Puerto Rican adults with DNA available, and extensive and detailed phenotypic data. To our knowledge, this is the largest cohort study of Puerto Ricans of this type. The genetics of this population has not been studied before to this extent and intensity, and this will, therefore, complement the goals ofthe GWAS consortium. We vAW focus on two prevalent conditions seen in excess in this population: hypertension and type 2 diabetes as it relates to cardiovascular disease (CVD). Within our NIH funded Center on Population Health and Health Disparities (CPHHD, 5P01-AG023394), we have a longitudinal study of 1450 Puerto Rican adults, aged 45-75 y. The study includes data on demographics, socio-economics, dietary intake and health behaviors, anthropometric measures, biochemistries and genot5q)es of over 150 genetic variants. Further, we have already completed 2-year-interviews of more than 900 subjects in our ongoing follow-up. GWAS will provide an efficient way to advance our understanding of health disparities and, as a population with excess risk, to identify novel genetic contributors to these conditions. Using GWAS in conjunction with in-depth bioinformatic analyses, we will further prioritize 450 SNPs that are associated with CVD and risk. Selected SNPs will be replicated in other two populations: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN), for which a GWAS is being conducted in our laboratotory, and the Nutrition, Aging, and Memory in Elders Study (NAME), an elderly cohort which has enriched phenotypes for vascular health and high prevalance of h3T)ertension and diabetes. Building on findings from the four other projects, we will explore genotype interaction with environmental variables, including diet, physical activity, acculturation and measures of stress to increase understanding ofthe risk of CVD. While the population size may appear small, the high prevalence of chronic diseases, such as hypertension and diabetes in this population and our success in detecting genetic associations for CVD and risk demonstrate the sufficient power of this population for GWAS. The findings from this study combined with those ofthe four other projects vnll allow us to (1) provide a fiill spectrum of genetic characteristics of CVD of this population; (2) create the foundation for a new understanding of health disparities in terms of genetics and environment (diets and lifestyle); (3) confirm potential genetic relationships in two additional populations.