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研究(GOCADAN)一直在通过对居住在诺顿湾地区诺姆镇和八个村庄的爱斯基摩人进行家庭遗传学研究，来研究心血管疾病及其风险因素。本申请建议扩展GOCADAN研究以追求以下目标：1)扩展将重点放在基因组扫描方法上的遗传学研究。1214名成员的完整基因组扫描，几乎都是一个扩展家系的一部分，将被用于识别亚临床心血管疾病和心血管疾病风险因素的数量性状基因座，并缩小感兴趣的区域，进行精细定位。2)重新检查家庭成员，以便分析风险因素的变化，并估计基因对变化的影响。将开始对心血管事件进行监测，包括年度死亡监测和对复查时发现的非致命事件的跟踪。GOCADAN的优势包括：1)它提供有关服务不足的民族的健康数据。2)大的家系扩大增加了发现亚临床脑血管病及其危险因素的重要基因座的机会。3)颈动脉超声测量的数据将有助于加深对血管疾病机制和心血管疾病遗传学的了解。4)一组独特的危险因素，几种危险因素的发生率较低，如糖尿病和高血压，但炎症水平和吸烟率较高，提供了一个独特的适合研究炎症标志物在心血管疾病中的作用的人群。GOCADAN将为肥胖、糖尿病和心血管疾病流行病迅速增加的美国和世界各地的这类人群和其他人群领导有价值的治疗和预防战略。

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.