NHLBI Family Blood Pressure Program: Methodology and recruitment in the HyperGEN network
NHLBI Family Blood Pressure Program: Methodology and recruitment in the HyperGEN network
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DOI：
10.1016/s1047-2797(00)00063-6
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发表时间：
2000-08-01
影响因子：
5.6
通讯作者：
Hunt, SC
中科院分区：
文献类型：
--
作者：
Williams, RR;Rao, DC;Hunt, SC
目得：高血压是严重疾病的常见前兆，包括白人中的中风、心肌梗死、充血性心力衰竭和肾衰竭，并且在更大程度上在非裔美国人中。大的遗传流行病学研究高血压需要获得的信息，将改善未来的方法，诊断，治疗和预防高血压，心血管疾病的发病率和mortals.METHODS的一个主要贡献者：我们报告成功实施了一个新的结构的研究合作，涉及四个NHLBI的“网络”，协调下的家庭血压计划。高血压遗传流行病学网络（HyperGEN）涉及来自六所大学和NHLBI的科学家，他们寻求识别和表征促进高血压的基因。血液样本和临床数据预计将从2244名60岁之前诊断为高血压的兄弟姐妹中收集，这些兄弟姐妹来自960名有两个或更多受影响者的兄弟姐妹（一半是非洲裔美国人）。超过100万个基因型测定（20个候选位点和387个匿名标记位点）的非参数同胞连锁分析预计有足够的权力检测遗传位点促进高血压。对于在本研究中显示连锁证据的基因座和其他组报告的与高血压连锁或相关的基因座，将高血压病例与基于人群的对照组的基因型进行比较，以鉴定或确认与高血压相关的遗传变异。对于一些与高血压相关的遗传变异，未治疗的成年后代携带者与非携带者的详细生理和生化特征可能有助于阐明促进高血压的病理生理机制。超过了2244名高血压参与者的预期样本量，对来自917个同胞的2407名高血压患者（1262名非洲裔美国人和1145名白人）进行了检查。详细的同意书旨在为参与者提供几种DNA测试的选择; 94%的参与者允许现在或将来进行任何机密医学研究的DNA测试，只有6%的人要求限制对他们的DNA进行测试。由于这是一项家庭研究，参与者还被要求列出所有一级亲属（沿着姓名、地址和电话号码），并为每个亲属指明他们是否愿意允许研究人员进行联系。70%的人允许联系一些亲属;大约30%的人允许联系所有一级亲属;不到1%的人要求不联系亲属。本研究前四年取得的成功包括：1）来自六个不同地点的八个中心的富有成效的合作; 2）早期实现了包括非裔美国人在内的研究参与者的招募目标; 3）DNA测试的同意率令人鼓舞4）完成了几个候选基因标记和多态性的遗传连锁和关联分析; 5）完成基因分型的随机标志物的一半以上的完整样本;和6）早期共享的结果之间的四个家庭血压计划网络的候选人和基因组搜索analysis.CONCLUSIONS：四年后的经验，这五年的计划（1995-2000年）表明，新发起的NHLBI网络计划机制是满足许多的期望，它的设计。它可以作为未来遗传学研究的范例，可以受益于大样本量，实验室之间频繁的想法共享，以及早期发现的及时独立确认，这是寻找具有相对较小影响的常见基因所必需的，例如那些易患人类高血压的基因。Ann Epidemiol 2000;10：389-400.出版社：Elsevier Science Inc.
PURPOSE: Hypertension is a common precursor of serious disorders including stroke, myocardial infarction, congestive heart failure, and renal failure in whites and to a greater extent in African Americans. Large genetic-epidemiological studies of hypertension are needed to gain information that will improve future methods for diagnosis, treatment, and prevention of hypertension, a major contributor to cardiovascular morbidity and mortality.METHODS: We report successful implementation of a new structure of research collaboration involving four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six universities and the NHLBI who seek to identify and characterize genes promoting hypertension. Blood samples and clinical data were projected to be collected from a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships (half African-American) with two or more affected persons. Nonparametric sibship linkage analysis of over one million genotype determinations (20 candidate loci and 387 anonymous marker loci) was projected to have sufficient power for detecting genetic loci promoting hypertension. For loci showing evidence for linkage in this study and for loci reported linked or associated with hypertension by other groups, genotypes are compared in hypertensive cases Versus population-based controls to identify or confirm genetic variants associated with hypertension. For some of these genetic variants associated with hypertension, detailed physiological and biochemical characterization of untreated adult offspring carriers versus non-carriers may help elucidate the pathophysiological mechanisms that promote hypertension.RESULTS: The projected sample size of 2244 hypertensive participants was surpassed, as 2407 hypertensive individuals (1262 African Americans and 1145 whites) from 917 sibships were examined. Detailed consent forms were designed to offer participants several options for DNA testing; 94% of participants gave permission for DNA testing now or in the future for any confidential medical research, with only 6% requesting restrictions for tests performed on their DNA. Since this is a family study, participants also are asked to list all first degree relatives (along with names, addresses, and phone numbers) and to indicate for each relative whether they were willing to allow study staff to make a contact. Seventy percent gave permission to contact some relatives; about 30% gave permission to contact all first degree relatives; and less than 1% asked that no relatives be contacted. Successes after the first four years of this study include: 1) productive collaboration of eight centers from six different locations; 2) early achievement of recruitment goals for study participants including African-Americans; 3) an encouraging rate of consent for DNA testing (including future testing) and relative contacting; 4) completed analyses of genetic linkage and association for several candidate gene markers and polymorphisms; 5) completed genotyping of random markers for over half of the full sample; and 6) early sharing of results among the four Family Blood Pressure Program networks for candidate and genome search analyses.CONCLUSIONS: Experience after four years of this five-year program (1995-2000) suggests that the newly initiated NHLBI Network Program mechanism is fulfilling many of the expectations for which it was designed. It may serve as a paradigm for future genetic research that can benefit from large sample sizes, frequent sharing of ideas among laboratories, and prompt independent confirmation of early findings, which are required in the search for common genes with relatively small effects such as those that predispose to human hypertension. Ann Epidemiol 2000;10:389-400. Published by Elsevier Science inc.