MESA Family Study

描述（由申请人提供）：这是梅萨系列研究HL 071205的首次重新提交。拟议的梅萨家族研究的总体目标是在美国少数民族人群中通过冠状动脉钙（CAC）和颈动脉内膜中层壁厚度（IMT）评估，定位和鉴定导致亚临床心血管疾病（CVD）的基因。这些目标将在一项研究中解决的2700个人从900个同胞（sibtrios或更大），均匀分布在非洲裔美国人和西班牙裔美国人，利用现有的框架NHLBI多种族研究的动脉粥样硬化（梅萨）。在目标1中，梅萨家族研究将确定这两个人群中CAC（EBCT和螺旋门控CT扫描）和IMT（B型超声）变异的遗传贡献程度。这一目标将通过对来自900例梅萨指数病例的1800名兄弟姐妹进行检查（表型分型）来实现（平均分为非洲裔美国人和西班牙裔美国人）。在目标2中，人类基因组中与这些定量亚临床心血管疾病特征（冠状动脉钙和IMT）相关的生物候选区域将通过基因组扫描方法进行鉴定，包括最佳区域的精细定位。这一目标将利用梅萨研究资源（数据协调中心、中心实验室、CT和超声阅读中心、6个临床现场中心）以及Cedars-Sinai医学中心和Wake-Forest医学院的综合资源和心血管遗传流行病学专业知识。在目标3中，基因定位和鉴定将通过来自梅萨的3个少数群体（非洲裔美国人、西班牙裔美国人和华裔美国人）的受试者中的位置以及生物学候选基因的关联研究来完成。梅萨（母研究）的目的是评估亚临床CVD并确定多种族人群中的流行病学风险因素，而梅萨家族研究的目的是确定导致这些亚临床CVD风险因素的基因（数量性状基因座或QTL）。结合传统的危险因素评估，确定的遗传标记物应该是有用的血管疾病患者的管理。这些结果将允许有针对性的诊断测试和药理学干预，并确定可以从特定预防方案中受益的受试者，从而提高美国人群的整体健康水平。

DESCRIPTION (provided by applicant): This is a first resubmission of the MESA Family Study, HL071205. The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to sub-clinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT) in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios or larger), evenly distributed among African-Americans and Hispanic Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA). In Aim 1, the MESA Family Study will determine the extent of genetic contribution to variation in CAC (EBCT and helical-gated CT scan) and IMT (B-mode ultrasound) in these two populations. This aim will be accomplished by examination (phenotyping) of 1800 siblings from 900 MESA index cases (evenly divided between African-Americans and Hispanic-Americans). In Aim 2, biological candidate regions in the human genome linked to these quantitative sub-clinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches, including fine mapping of the best regions. This aim will use the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers) and the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine. In Aim 3, gene localization and identification will be accomplished by association studies of positional as well as biological candidate genes in the subjects from the 3 minority populations of MESA (African-Americans, Hispanic-Americans, and Chinese-Americans). Whereas the purpose of MESA (the parent study) is to assess sub-clinical CVD and identify epidemiological risk factors in multi-ethnic populations, the purpose of the MESA Family Study is to identify the genes (quantitative trait loci, or QTLs) that contribute to these sub-clinical CVD risk factors. In combination with traditional risk factor assessment, identified inherited markers should be useful in the management of patients with vascular disease. These results will permit targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols, thus result in an increase in the overall well being of the US population.