GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE (GENOA)

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况的变化。 这四个网络最初是单独出资和竞争的，但有两个 关键的认识导致了充分的合作和协作。第一, 血压控制的寡源性本质决定了大样本 是获得足够的基因组连锁和统计能力所必需的 关联性分析。第二，连锁区间较宽，包含较大的 基因的数量，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，而且是最好的 例如，该方案创建了汇集的数据集和协议 关于协调的出版物。 在最初的筹资期间，该方案超过了最初的 招募目标，进行了多个全基因组范围的连锁和关联 分析并创建了一个临时集合数据集，其中包含表型和 来自10,000多个个体的基因数据。在此续签申请中， 该计划提出了五个具体目标，这四个目标都将由这四个机构执行 网络。这些目标可以根据两个相辅相成的主题进行分组： 首先，这些申请者将创建和分析血压数据库- 所有FBPP参与者的相关表型和基因数据(目标1)。 在相关联的区域内，他们将识别位置上的等位基因变异 候选基因，并评估这些多态与 血压水平和高血压状况(目标2和3)。第二，他们 将使用靶器官损伤的定量测量来识别 影响高血压性心脏和肾脏疾病的易感性 (目标4和5)。除了计划的特定目标外，每个网络 提出由该网络单独执行的具体目标，基于 他们人口的独特方面以及他们的兴趣和专业知识 调查人员。 家庭血压计划代表了最坚定的 高血压遗传学的多学科研究。 由此产生的想法和积累的数据的综合使得严格的假设成为可能 测试是不可能的，并将加速理解以前的 导致疾病风险的难以捉摸的基因变异。

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.