GENCAC - Framingham Field Center

GENCAC - 弗雷明汉现场中心

• 批准号: 6792770
• 负责人: R. Curtis Ellison
• 金额: $ 13.92万
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792770
• 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），是为了确定遗传因素，建立 对（a）冠状动脉和主动脉粥样硬化的易感性和（B）个体间 炎症反应的可变性。我们建议量化 冠状动脉和主动脉钙化量在441选定，信息 既往检查和广泛基因分型的家系（约3，000人） （跨越基因组的约400个标记），以 来鉴定与人类动脉粥样硬化相关的基因。额外275 非裔美国人的同胞（约600人，也检查和分析） 基因分型）将被纳入，以解决这些研究问题，在这一高风险 人口个体间变异性评估 炎症负荷和宿主反应，以及广泛的代谢， 行为和环境数据已经收集这些谱系将 提供增强的表型同质性和增加的分析能力， 评估动脉粥样硬化的遗传基础。 将使用最先进的实验室和统计方法来发现， 定位和表征易感基因的影响， 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、遗传和种群问题 异质性，上位性，遗传和 环境风险因素，并优化基因组区域的检测 影响表型易感性。臭名昭著的多重性问题 基因组扫描中的比较将通过使用新的全局 试验程序. 基于信息谱系的成本效益设计和采用新颖的 方法，这项研究将有助于目前无法获得的信息， 动脉粥样硬化的遗传和环境决定因素，重点是 预防这种广泛流行的疾病与高负担的 社会的成本。