GENETIC DETERMINANTS OF HIGH BP IN THREE RACIAL GROUPS

三个种族群体中高血压的遗传决定因素

• 批准号: 6604272
• 负责人: Robert Edward Ferrell
• 金额: $ 15.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-05 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604272
• 关键词: African American; Mexican Americans; blood pressure; cardiovascular disorder epidemiology; caucasian American; clinical research; cooperative study; family genetics; genetic polymorphism; genetic susceptibility; genotype; human genetic material tag; human subject; hypertension; linkage mapping; phenotype; racial /ethnic difference

The NHLBI Family Blood Pressure Program is made up of four cooperating networks whose overall objective is to localize and characterize genes contributing to variation in blood pressure levels and hypertension status. The four networks were originally separately funded and competitive, but two critical realizations have led to full cooperation and collaboration. First, the oligogenic nature of blood pressure control dictates that large samples are necessary to achieve adequate statistical power for genomic linkage and association analyses. Second, linkage intervals are broad and contain large numbers of genes, so that success in identifying genes and mutations requires the effort of multiple laboratories freely sharing information. This coordination extends far beyond phenotyping and genotyping and is best exemplified by the Program's creation of a pooled data set and agreements about coordinated publications. During the initial funding period, the Program surpassed its original recruitment goals, carried out multiple genome-wide linkage and association analyses and created an interim pooled data set consisting of phenotype and genotype data from more than 10,000 individuals. In this renewal application, the Program proposes five specific aims to be carried out by all four networks. These aims can be grouped according to two complementary themes: First, these applicants will create and analyze a database of blood pressure- related phenotype and genotype data from all FBPP participants (Aim 1). Within linked regions, they will identify allelic variation within positional candidate genes and evaluate the relationship of these polymorphisms with blood pressure levels and hypertension status (Aims 2 and 3). Second, they will use quantitative measures of target organ damage to identify genes that influence susceptibility to develop hypertensive heart and kidney diseases (Aims 4 and 5). In addition to the Program specific aims, each network proposes specific aims to be carried out by that network alone, based on unique aspects of their population and interests and expertise of the investigators. The Family Blood Pressure Program represents the most determined multidisciplinary approach to the genetics of hypertension ever assembled. The resulting synthesis of ideas and amassed data permits rigorous hypothesis testing not otherwise possible and will hasten understanding of the previously elusive genetic variation responsible for disease risk.

NHLBI 家庭血压计划由四个合作伙伴组成 其总体目标是定位和表征基因的网络 导致血压水平和高血压状态的变化。 这四个网络原本是各自资助且相互竞争的，但两个网络 重要的认识导致了充分的合作与协作。 第一的， 血压控制的寡基因性质决定了大样本 为获得足够的基因组连锁统计能力所必需的 关联分析。 其次，连锁区间广泛且包含大量 基因数量，因此成功识别基因和突变需要 多个实验室自由共享信息的努力。 这 协调远远超出了表型和基因分型的范围，并且是最好的 以该计划创建汇集数据集和协议为例 关于协调出版物。 在最初的资助期间，该计划超越了最初的目标 招募目标，进行多个全基因组连锁和关联 分析并创建了一个由表型和 来自 10,000 多个个体的基因型数据。 在这份续签申请中， 该计划提出了由所有四个机构共同实现的五个具体目标 网络。 这些目标可以根据两个互补的主题进行分组： 首先，这些申请人将创建并分析血压数据库 - 来自所有 FBPP 参与者的相关表型和基因型数据（目标 1）。 在链接区域内，他们将识别位置内的等位基因变异 候选基因并评估这些多态性与 血压水平和高血压状况（目标 2 和 3）。 其次，他们 将使用靶器官损伤的定量测量来识别基因 影响患高血压、心脏和肾脏疾病的易感性 （目标 4 和 5）。 除了该计划的具体目标外，每个网络 提出了由该网络单独实现的具体目标 他们的人口以及兴趣和专业知识的独特方面 调查人员。 家庭血压计划代表了最坚定的 有史以来对高血压遗传学进行多学科研究的方法。 由此产生的想法和积累的数据的综合允许严格的假设 否则不可能进行测试，并且将加速对先前内容的理解 难以捉摸的遗传变异导致疾病风险。