HYPERGEN

包括波士顿在内的9个中心的遗传流行病学网络 大学/法国，将研究遗传和相互作用的非遗传 高血压的决定因素先前收集的高血压数据 在来自Fragmentary研究的白色受试者中， 家庭心脏研究，以及其他研究中心的黑人受试者， 对黑人家庭和非黑人家庭进行大量平等抽样鉴定 有2+高血压兄弟姐妹，未接受治疗的亲属和对照（总计 4，600名受试者）进行遗传关联和亲缘关系研究（以 测试20个候选基因和匿名标记，总计约75万个 基因型测定）;以及丰富的流行病学电池 分析评估家族史和基因型信息的组合 重要的非遗传因素。 数据协调中心，四个外地中心（包括法兰克福）， 家庭心脏研究（“FHS”）的生物化学实验室中心加上两个 另外的黑场中心和DNA实验室中心形成了这个网络。的 该网络的调查人员已经发表了关于 高血压的遗传学和流行病学以及最先进的技术 在分子生物学、生物化学、流行病学和 遗传流行病学统计学。这些调查人员有一个证明 各机构之间富有成效的合作的记录。研究 本提案中的设计充分利用了 在这个网络内，以及在这个网络和其他网络之间， 同样的合作协议。 从超过20，000个筛选的先证者的组合基础人群中， 在1200个兄弟姐妹中，有两个或更多的兄弟姐妹被编入索引， 60岁以前诊断的高血压。这些兄弟姐妹被选中 按种族（黑人和非黑人）平均分为若干小组， 高血压的严重程度（重度和轻度），可进一步分层 其他相关因素（体重指数、血脂、发病年龄 高血压等）。方法的选择（遗传关联和 无模型亲缘关系）和大样本量，具有分析能力 在更同质的亚组中提供了良好的功效来检测特定的 遗传位点促进高血压，尽管有相当大的异质性。 在独立人群中进行的重复研究（这些受试者与 先前研究犹他州的兄弟关系和其他合作网络） 将允许确认基因的遗传位点， 高血压其他网络发现的位置也将在 我们的实验对象进行确认流行病学分析 如果没有一个或多个已证实的高血压基因， 与非遗传因素和中间表型将确定基因- 环境相互作用和特定的生活方式因素， 缺席似乎有助于确定表达特定 高血压的遗传易感性

A genetic epidemiology network of 9 centers, including Boston University/Framingham, will study genetic and interacting non-genetic determinants of hypertension. Previously collected data on hypertension and family history in white subjects from the Framingham Study and the Family Heart Study, and in black subjects at other sites, allow the identification of a large and equal sample of black and non-black families with 2+ hypertensive siblings, untreated relatives and controls (total 4,600 subjects) for genetic association and sibship linkage studies (to test 20 candidate genes and anonymous markers totalling about 750,000 genotype determinations); as well as a rich battery of epidemiologic analyses assessing family history and genotype information in combination with important non-genetic factors. The data coordinating center, four field centers (including Framingham), and biochemistry lab center of the Family Heart Study ("FHS") plus two additional black field centers and DNA lab center form this network. The investigators in this network have published major findings regarding the genetics and epidemiology of hypertension and state-of-the-art technology in molecular biology, biochemistry, epidemiology, and specialized statistics for genetic epidemiology. These investigators have a proven track record of productive collaboration between institutions. The study design in this proposal takes full advantage of strong collaboration both within this network and between this and other networks operating under the same cooperative agreement. From a combined base population of over 20,000 screened probands, a sample of l,200 sibships have been indexed with two or more siblings having hypertension diagnosed before age 60. These sibships have been chosen to be equally divided into subgroups by race (black and non-black) and severity of hypertension (severe and mild) and can be further stratified by other pertinent factors (body mass index, plasma lipids, age of onset of hypertension, etc.). The choice of methods (genetic association and model-free sibship linkage) and large sample size with ability to analyze within more homogeneous subgroups provide good power to detect specific genetic loci promoting hypertension despite considerable heterogeneity. Replication studies in independent populations (these subjects versus previously studies Utah sibships and versus other collaborative Networks) will allow the confirmation of genetic loci for genes promoting hypertension. Loci found by other networks will also be rapidly tested in our subjects for confirmation. Epidemiological analyses of persons with and without one or more confirmed genes for hypertension in combination with non-genetic factors and intermediate phenotypes will identify gene- environment interactions and specific lifestyle factors whose presence or absence seem to help determine the likelihood of expressing specific genetic predispositions to hypertension.