Family Blood Pressure Program (GenNet Network)

描述(由申请人提供)： 家庭血压计划[FBPP]是一项史无前例的合作，旨在确定影响血压水平、高血压及其心血管并发症的基因(以下称为高血压基因)。到目前为止，该计划已经进行了2.16万次体检，建立了294个高血压相关变量的共享数据库，测量了7321个人的定量超声心动图，对高血压状况和13个相关表型进行了全基因组连锁分析，发表(或印刷)了128篇手稿，并通过跟踪4个连锁高峰确定了5个高血压易感基因。在拟议的FBPP的下一阶段，一个主要的重点是使该计划成为美国和世界各地高血压研究人员的共享资源。在目标1中，我们将建立、维护和更新一个公开可用的知识库，以促进非FBPP调查人员对高血压的遗传学、其危险因素及其并发症的研究。在目标2中，我们将使用最先进的遗传连锁分析方法，通过家系亚组和生理上相关的表型组合来识别额外的连锁区域，这将有助于定位高血压基因。在目标3中，我们将使用生物信息学、密集的SNP阵列和最先进的技术相结合 数据分析，以跟踪感兴趣的区域，并确定潜在的高血压基因。需要采取后续行动的区域包括在FBPP当前阶段和这一更新阶段的目标2中确定的区域。在目标4中，我们将评估目标3中确定的高血压基因与反映高血压心血管和肾脏并发症的多种指标的相关性，包括左心室重量和微量白蛋白尿。FBPP的长期目标是让高血压遗传学社区全面了解人类高血压的遗传结构，包括其危险因素、并发症和对治疗的反应。 (摘要结束)

DESCRIPTION (provided by applicant): The Family Blood Pressure Program [FBPP] is an unprecedented collaboration to identify genes influencing blood pressure levels, hypertension and its cardiovascular complications (hereafter referred to as "hypertension genes"). To date, the Program has carried out 21,600 physical examinations, assembled a shared database of 294 hypertension-relevant variables, measured quantitative echocardiograms on 7,321 individuals, carried-out genome-wide linkage analyses for hypertension status and 13 related phenotypes, published (or in press) 128 manuscripts and identified 5 hypertension susceptibility genes by following-up 4 linkage peaks. In the proposed next phase of the FBPP, a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world. In Aim 1, we will build, maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension, its risk factors and its complications. In Aim 2, we will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes. In Aim 3, we will use a combination of bioinformatics, a dense array of SNPs, and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes. The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase. In Aim 4, we will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension, including left ventricular mass and microalbuminuria. It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension, including its risk factors, complications, and response to treatment. (End of Abstract)