Cardiovascular Disease in Sioux Indians

心血管疾病(CVD)在美洲印第安人中流行。强心研究(SHS)一直在通过在3个地理区域(亚利桑那州、达科他州和俄克拉何马州)的13个社区进行纵向队列研究和家庭遗传学研究来检查心血管疾病及其危险因素。本申请建议扩展SHS以实现以下目标：1)扩大遗传学研究，强调基因组扫描方法，但也包括对精心挑选的候选基因的调查。来自94个大家庭的3776名成员的完整基因组扫描将用于识别数量性状基因座，并通过精细作图缩小感兴趣区域。我们还将检查选定的一些候选基因，这些基因在连锁研究的基础上很难排除，但对血管疾病具有潜在的重要性。(2)继续对原队列(约2859名男性和女性幸存者，年龄60-89岁)进行死亡率和发病率监测，并启动对非队列家庭成员的年度死亡率监测和有限发病率后续行动。3)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。 SHS的优势包括：1)提供服务不足种族的健康数据；2)这是美国规模最大、持续时间最长的关于心血管疾病及其糖尿病患者风险因素的纵向研究；3)心脏、颈动脉和踝部超声测量的数据将大大提高对糖尿病血管疾病机制和心血管疾病遗传学的了解；4)这一人群包括肥胖和糖尿病的流行在很小的年龄就影响到人们的人群，使得能够分析这些疾病的遗传和环境影响，以及年龄影响的有限混淆。SHS将为美国和世界上肥胖、糖尿病和心血管疾病流行迅速发展的这一人群和其他人群带来有价值的治疗和预防战略。

There is an epidemic of cardiovascular disease (CVD) among American Indians. The Strong Heart Study (SHS) has been examining CVD and its risk factors by conducting a longitudinal cohort study and a family genetic study among 13 communities in 3 geographic areas (Arizona, the Dakotas, and Oklahoma). This application proposes to extend the SHS to pursue the following aims: 1) Expand the genetic studies that will emphasize the genome scan approach, but also include investigation of carefully selected candidate genes. The completed genome scan of 3776 members from 94 extended families will be used to identify quantitative trait loci and narrow the regions of interest by fine mapping. We also will examine a selected number of candidate genes that are difficult to exclude on the basis of linkage studies, but are of potential importance to vascular disease. 2) Continue the mortality and morbidity surveillance of the original cohort (approximately 2859 male and female survivors, ages 60-89 years) and to initiate annual mortality surveillance and limited morbidity follow-up of the non-cohort family members. 3) Re-examine the family members so that changes in risk factors can be analyzed and genetic effects on changes estimated. Advantages of the SHS include: 1) It provides health data on an underserved ethnic group, 2) It is the largest, longest longitudinal study in the US of CVD and its risk factors in individuals with diabetes, 3) Data from cardiac, carotid, and popliteal ultrasound measures will substantially improve understanding of mechanisms of vascular disease in diabetes and the genetics of CVD, 4) This population includes a group in which the epidemic of obesity and diabetes has impacted people at very young ages, permitting analysis of genetic and environmental effects on these conditions with limited confounding by age effects. SHS will lead to valuable therapeutic and prevention strategies for this and other populations in the US and the world, where the epidemics of obesity, diabetes and CVD are progressing rapidly.