GENCAC - Framingham Field Center

GENCAC - 弗雷明汉现场中心

• 批准号: 6527759
• 负责人: R. Curtis Ellison
• 金额: $ 35.51万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-17 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527759
• 关键词: African American; aorta disorder; atherosclerosis; calcification; cardiovascular disorder epidemiology; clinical research; cooperative study; coronary disorder; family genetics; gene environment interaction; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human subject; inflammation

DESCRIPTION (provided by applicant) The purpose of the proposed study, Genetics of Coronary and Aortic Calcification (GENCAC), is to identify genetic factors that establish susceptibility to (a) coronary and aortic atherosclerosis and (b) inter-individual variability in the inflammatory response. We propose to quantify coronary and aortic artery calcium volume in 441 selected, informative pedigrees (~ 3,000 individuals) previously examined and extensively genotyped (~400 markers spanning the genome) by the NHLBI Family Heart Study, in order to identify genes associated with human atherosclerosis. An additional 275 African American sibships (~600 individuals, also examined and comparably genotyped) will be included to address these study questions in this high-risk population. Assessment of the inter-individual variability in the inflammatory burden and the host response, and the extensive metabolic, behavioral, and environmental data already collected on these pedigrees will provide enhanced phenotypic homogeneity and increased analytic power in assessing the genetic basis of atherosclerosis. State of the art laboratory and statistical methods will be used to find, localize and characterize the influence of predisposing genes to atherosclerosis and the inflammatory response. 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 phenotypic susceptibility. The notorious issue of multiple comparisons in genome scans will be bypassed with the use of novel global testing procedures. Based on a cost-efficient design of informative pedigrees and employing novel methodology, this study will contribute currently unavailable information on genetic and environmental determinants of atherosclerosis, with a focus on the prevention of this widely prevalent condition associated with high burden of costs to society.

描述（由申请人提供） 拟议研究的目的，冠状动脉和主动脉的遗传学 钙化（GENCAC）是确定建立的遗传因素 对（a）冠状动脉和主动脉粥样硬化和（b）个体敏感性 炎症反应的可变性。我们建议量化 冠状动脉和主动脉动脉钙量441位选定，信息丰富 先前检查和广泛基因分型的血统（约3,000个人） （跨基因组的400个标记）由NHLBI家庭心脏研究，按顺序 鉴定与人动脉粥样硬化有关的基因。另外275 非洲裔美国人（约600个人，也接受了检查且相当 基因分型）将包括在此高风险中解决这些研究问题 人口。评估个体间变异性 炎症负担和宿主反应，以及广泛的代谢， 行为和已经在这些血统上收集的环境数据将 提供增强的表型均匀性并提高分析能力 评估动脉粥样硬化的遗传基础。 最先进的实验室和统计方法将用于查找， 本地化并表征诱发基因对 动脉粥样硬化和炎症反应。新的遗传分析方法 将用于解决表型，遗传和人口的问题 异质性，上毒，遗传和遗传之间的复杂相互作用 环境风险因素，并优化基因组区域的检测 影响表型敏感性。臭名昭著的多重问题 基因组扫描中的比较将随着新型全局的使用而绕开 测试程序。 基于信息丰富的谱系的成本效益设计并采用小说 方法论，这项研究将为目前无法提供有关 动脉粥样硬化的遗传和环境决定因素，重点是 预防这种广泛普遍的条件与高负担有关 向社会成本。