FHS-Molecular Genetics & Genetic Epidemiology

FHS-分子遗传学

• 批准号: 6495228
• 负责人: Michael A. Province
• 金额: $ 8.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6495228
• 关键词: atherosclerosis; biotechnology; cardiovascular disorder epidemiology; clinical research; coronary disorder; family genetics; gene environment interaction; genetic mapping; genetic markers; genetic susceptibility; human data

DESCRIPTION (Investigator's abstract): The primary goal of this renewal application from the NHLBI Family Heart Study (FHS) investigators is to identify the genomic regions linked and/or associated with CHD, atherosclerotic burden measured by ultrasound, and their risk factors. A secondary aim is to characterize interactions and the genetic epidemiology of CHD risk factors in terms of the identified genomic regions. The recently completed genome-wide scan, conducted upon large FHS samples of extended pedigrees, will allow detection of genes in the range of 10-15 percent (locus-specific) heritability. A third aim is to do a limited, focused amount of denser genotyping of markers in the most promising regions, to verify the results and begin to more precisely define the peaks. State of the art analytic methods and software will be applied, drawing on the complementary genetic epidemiology expertise assembled at five sites of the FHS, with scientific, analytic, and data management support from the FHS Coordinating Center. The plans are sharply focused on completing the analysis and publication of the genome scans. Novel genetic analysis methods will be used to address the issues of phenotypic, genetic and population heterogeneity, epistasis, complex interactions among the genetic and environmental risk factors, and to optimize the detection of genomic regions affecting CHD susceptibility and the risk factors. The notorious issue of multiple comparisons in genome scans will be bypassed altogether with the use of novel global testing procedures. During a previous funding cycle of the FHS, we extensively characterized the CHD and associated traits in subjects from 583 random sample pedigrees, 649 coronary heart disease (CHD)-prone pedigrees, and 59 African-American pedigrees (5,818 individuals) drawn from four epidenuologically defined populations, with banking of high quality DNA. Analysis and publication of these phenotypic data was actively pursued while genotyping was underway for selected candidate genes as well as for a coarse map of 244 Utah markers on 1,184 high risk siblings. Although not originally anticipated, an additional dense map of 404 markers is now available from the Mammalian Genotyping Service on 3,027 individuals from the 401 largest extended FHS pedigrees. Current funding expired in July 2000, too late to analyze this unanticipated genotyping that has now been completed on the majority of the largest and most informative FHS pedigrees. This extension will make this unique resource available for identifying genomic regions influencing a wide variety of CHD associated traits from all major risk factor domains.

描述(调查人员摘要)：此次更新的主要目标 NHLBI家庭心脏研究(FHS)调查人员的申请是 确定与冠心病、动脉粥样硬化相关和/或相关的基因组区域 超声测量的负荷量及其危险因素。第二个目标是 描述冠心病危险因素的相互作用和遗传流行病学 已识别的基因组区域的术语。最近完成的全基因组 对扩展家系的FHS大样本进行扫描，将允许 检测10-15%(特定于基因位点)的遗传力的基因。 第三个目标是有限的、集中的、更密集的标记基因分型。 在最有希望的地区，验证结果并开始更多 准确地定义峰值。最先进的分析方法和软件将 利用互补的遗传流行病学专业知识进行应用 在FHS的五个地点集合，提供科学、分析和数据 来自FHS协调中心的管理支持。这些计划是尖锐的 专注于完成基因组扫描的分析和发布。小说 遗传分析方法将被用来解决表型问题， 遗传和种群的异质性，上位性，以及 遗传和环境风险因素，并优化检测 影响冠心病易感性的基因组区域及其危险因素。这个 将绕过基因组扫描中的多重比较这一臭名昭著的问题 完全通过使用新颖的全球测试程序。在上一次 FHS的资金周期，我们广泛地描述了CHD和相关的 583个随机抽样家系、649个冠心病患者的遗传特征 (CHD)易患家系和59个非裔美国人家系(5818人) 从四个流行病定义的人群中提取，银行存款高 高质量的DNA。正在积极分析和公布这些表型数据 在对选定的候选基因进行基因分型的同时进行 查看1184名高危兄弟姐妹上244名犹他州标记的粗略地图。虽然不是 最初预计的是，现在可以使用由404个标记组成的额外密集地图 哺乳动物基因分型服务对来自401个最大的 扩大的FHS血统。目前的资金已于2000年7月到期，为时已晚 分析这一出乎意料的基因分型，现在已经在 大多数规模最大、信息量最大的FHS谱系。这一延期将 使这一独特的资源可用于识别影响 来自所有主要风险因素领域的各种与冠心病相关的特征。