GENCAC - Arterial Calcium Reading Center

这项名为“冠状动脉和主动脉钙化遗传学”(GENCAC)的研究旨在确定导致冠状动脉和主动脉粥样硬化以及宿主高炎性反应易感性的遗传因素。我们建议量化441个有信息的家系(3000人)的冠状动脉和主动脉钙容量，以确定与动脉粥样硬化相关的基因。另外275名非洲裔美国人的兄弟姐妹(-600人)将接受检查，以解决这一高危人群中的这些研究问题。将测量炎症细胞因子和炎症反应的标记物，以表征炎症负担和宿主反应。炎症宿主反应的个体间变异性，以及在FHS中收集的关于这些家系的广泛的代谢、行为和环境数据将提供增强的表型同质性和在评估动脉粥样硬化的遗传基础方面的分析能力。新的实验室方法和最新的统计学方法将用于发现、定位和表征易感基因对动脉粥样硬化和炎性宿主反应的影响，重点关注表型、遗传和群体异质性、上位性、遗传和环境风险因素之间的复杂相互作用，以及影响表型易感性的基因组区域的检测。这项研究的成本效益设计将基于同胞关系和大型家系，所有这些人都经过检查，并拥有可用的基因组扫描数据。这项研究将提供有关遗传变异以及与动脉粥样硬化易感性相关的上下文相关效应的新信息。动脉粥样硬化是美国头号死亡原因，也是我们社会医疗保健支出的主要驱动力。该申请对应于维克森林大学医学院提交的动脉钙阅读中心，该中心是GENCAC遗传流行病学网络的一部分。

The purpose of the proposed study, Genetics of Coronary and Aortic Calcification (GENCAC), is to identify genetic factors that establish susceptibility to coronary and aortic atherosclerosis and to the hyperinflammatory host response. We propose to quantify coronary and aortic artery calcium volume in 441 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 atherosclerosis. An additional 275 African American sibships (-600 individuals) will be examined to address these study questions in this high-risk population. Inflammatory cytokines and markers of the inflammatory response will be measured, to characterize both the inflammatory burden, and the host response. Interindividual variability in the inflammatory host response, and the extensive metabolic, behavioral, and environmental data collected on these pedigrees in the FHS will provide enhanced phenotypic homogeneity and increased analytic power in assessing the genetic basis of atherosclerosis. Novel laboratory methodology and state of the art statistical methods will be used to find, localize and characterize the influence of predisposing genes to atherosclerosis and the inflammatory host response, with attention to phenotypic, genetic and population heterogeneity, epistasis, complex interactions among the genetic and environmental risk factors, and the detection of genomic regions affecting phenotypic susceptibility. The cost-efficient design of this study will be based on sibships and large pedigrees, all of whom have been examined and have genome scan data available. This study will contribute new information on genetic variation, and context-dependent effects associated with susceptibility to atherosclerosis which is the number one cause of death in the U.S. and is the primary driver of health care expenditures in our society. This application corresponds to the Arterial Calcium Reading Center submitted by Wake Forest University School of Medicine as part of the GENCAC genetic epidemiology network.