HYPERGEN

由包括波士顿在内的9个中心组成的遗传流行病学网络 大学/弗雷明翰大学将研究遗传和相互作用的非遗传 高血压的决定因素。以前收集的高血压数据 来自弗雷明翰研究的白人受试者和 家庭心脏研究，以及其他网站的黑人受试者，允许 黑人和非黑人家庭的大样本和等量样本的鉴定 有2个以上的高血压兄弟姐妹、未经治疗的亲属和对照组(总计 4,600名受试者)，用于遗传关联和兄弟姐妹关系研究(至 测试20个候选基因和总计约750,000个匿名标记 基因分型)；以及丰富的流行病学资料 结合评估家族史和基因信息的分析 有重要的非遗传因素。 数据协调中心，四个外地中心(包括弗雷明翰)， 和家庭心脏研究生化实验室中心(FHS)外加两个 额外的黑场中心和DNA实验室中心形成了这个网络。这个 该网络的调查人员已经公布了关于 高血压的遗传学、流行病学和最新技术 分子生物学、生物化学、流行病学和专科 遗传流行病学的统计数据。这些调查人员已经证明了 各机构之间卓有成效的合作记录。这项研究 此方案中的设计充分利用了强大的协作能力 在此网络内以及在此网络和在 同样的合作协议。 从20,000多名经过筛查的先证者的综合基础人口中， 在L中，已有200个兄弟姐妹被索引，其中有两个或更多兄弟姐妹具有 60岁以前确诊的高血压患者。这些兄弟会被选中是为了 按种族(黑人和非黑人)平均分为小组和 高血压的严重程度(重度和轻度)，并可以进一步分层 按其他相关因素(体重指数、血脂、发病年龄 高血压等)。方法的选择(遗传关联和 无模型兄弟关系链接)和具有分析能力的大样本容量 在更同质的子组中提供了很好的能力来检测特定的 尽管存在相当大的异质性，但遗传基因座仍促进高血压。 独立人群中的复制研究(这些受试者与 以前研究过犹他州兄弟关系和与其他协作网络的对比) 将允许确认促进基因的遗传位点 高血压。其他网络发现的基因座也将在 我们的目标等待确认。慢性阻塞性肺病患者流行病学分析 并且没有一个或多个已确认的高血压基因组合 具有非遗传因素和中间表型的人将识别基因- 环境相互作用和特定生活方式因素，其存在或 缺席似乎有助于确定表达特定信息的可能性 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.