GWAS FOR CARDIOVASCULAR HEALTH IN ELDERLY PUERTO RICANS

基因分析的快速发展揭开了人口健康令人振奋的篇章。那里有 关于潜在影响健康结果的基因和多态基因的报告大幅增加。 特别是，全基因组扫描技术和生物信息学正在提供令人兴奋的信息 疾病风险。然而，大多数可用数据，特别是全基因组关联(GWAS)研究，是 基于非西班牙裔白人人口。随着美国拉美裔人口的预计增长和 鉴于这一人群中健康差距的扩大，将其纳入基因研究势在必行。我们为您提供一个 独特的资源，因为我们有一群拥有DNA的波多黎各成年人，而且 详细的表型数据。据我们所知，这是对这种类型的波多黎各人进行的最大规模的队列研究。这个 这一群体的遗传学以前从未被研究到这样的程度和强度，因此， 补充全球气候变化联盟的目标。我们VAW关注的是两种普遍存在的情况 这一人群：高血压和2型糖尿病，因为它与心血管疾病(CVD)有关。在我们的 美国国立卫生研究院资助的人口健康和健康差距中心(CPHHD，5P01-AG023394)，我们有一个 对1450名45-75岁的波多黎各成年人进行了纵向研究。这项研究包括人口统计学数据， 社会经济、饮食摄入量和健康行为、人体测量、生物化学和 超过150个遗传变异的基因。此外，我们已经完成了为期两年的采访 900名受试者在我们正在进行的跟踪调查中。全球气候变化网络将提供一种有效的方式来促进我们对 健康差异，以及作为风险过高的人群，找出导致这些差异的新的基因因素 条件。结合深入的生物信息学分析，我们将进一步优先考虑450个 与心血管疾病和风险相关的单核苷酸多态。选定的SNPs将在其他两个群体中复制： 降脂药物遗传学与饮食网络(GOLDN)，其中GWA正在我们的 实验室和老年人研究中的营养、衰老和记忆(NAME)，这是一个老年人队列，有 丰富的表型有助于血管健康和H3T的高患病率)高血压和糖尿病。在基础上建设 来自其他四个项目的发现，我们将探索基因与环境变量的相互作用， 包括饮食、体力活动、文化适应和压力措施，以增加对糖尿病风险的了解 心血管疾病。虽然人口规模可能看起来很小，但慢性病的高流行率，如 这一人群中的高血压和糖尿病，以及我们在检测心血管疾病和糖尿病遗传相关性方面的成功 风险证明了这一群体对全球气候变化的足够能力。这项研究的发现结合在一起 与其他四个项目一起，我们将能够(1)提供完整的遗传特征谱 心血管疾病；(2)为从以下方面重新理解健康差距奠定基础 遗传学和环境(饮食和生活方式)；(3)在另外两个 人口。

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.