Genetics of Coronary Artery Disease in Alaska Natives (*

描述（由申请人提供）： 心血管疾病（CVD）在阿拉斯加原住民中正在增加。阿拉斯加原住民冠状动脉疾病遗传学（GOCADAN）研究通过对居住在诺顿湾地区八个村庄和诺姆镇的爱斯基摩人进行家庭遗传学研究，检查了CVD及其危险因素。本申请建议扩展GOCADAN研究，以实现以下目标：1）扩大强调基因组扫描方法的遗传学研究。1,214名成员的全基因组扫描几乎都是一个扩展谱系的一部分，将用于确定亚临床CVD和CVD风险因素的数量性状基因座，并通过精细定位缩小感兴趣的区域。2)重新检查家庭成员，以便分析危险因素的变化，并估计遗传对变化的影响。心血管疾病事件的监测将建立起来，包括每年的死亡率监测和随访复查时发现的非致命性事件。GOCADAN的优点包括：1）它提供了一个服务不足的种族群体的健康数据。2)大的扩展谱系提高了检测亚临床CVD及其危险因素的重要位点的机会。3)颈动脉超声测量的数据将提高对血管疾病机制和CVD遗传学的理解。4)一个独特的风险因素的星座与低利率的几个风险因素，如糖尿病和高血压，但高水平的炎症和吸烟率，提供了一个独特的人群适合检查炎症标志物在CVD中的作用。GOCADAN将领导美国和世界上肥胖、糖尿病和心血管疾病流行迅速增加的这类人群和其他人群的有价值的治疗和预防策略。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is increasing among Alaska Natives. The Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study has been examining CVD and its risk factors by conducting a family genetic study among Eskimos residing in eight villages and the town of Nome in the Norton Sound Region. This application proposes to extend the GOCADAN study to pursue the following aims: 1) Expand the genetic studies that will emphasize the genome scan approach. The complete genome scan of 1,214 members, who are nearly all part of one extended pedigree, will be used to identify quantitative trait loci for subclinical CVD and CVD risk factors and narrow the regions of interest be fine mapping. 2) Re-examine the family members so that changes in risk factors can be analyzed and genetic effects on changes estimated. Surveillance for CVD events will be instituted, including annual mortality surveillance and follow-up of nonfatal events uncovered at the time of the re-exam. Advantages of GOCADAN include: 1) It provides health data on an underserved ethnic group. 2) The large extended pedigree improves the chances of detecting significant loci for subclinical CVD and its risk factors. 3) Data from carotid ultrasound measures will improve understanding of mechanisms of vascular disease and the genetics of CVD. 4) A unique constellation of risk factors with low rates of several risk factors, such as diabetes and hypertension, but high levels of inflammation and rates of smoking, provides a population uniquely suited to examine the roles of inflammatory markers in CVD. GOCADAN will lead the valuable therapeutic and prevention strategies for this and other populations in the United States and the world, where the epidemics of obesity, diabetes, and CVD are increasing rapidly.