MESA Family Study

描述（由申请人提供）：拟议的梅萨家族研究的总体目标是通过冠状动脉钙（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，并评估生活方式和环境对美国少数民族人群中CVD遗传易感性表现的影响。这些目标将在2700人的研究中得到解决，从900个同胞（sibtrios），均匀分布在非洲裔美国人，西班牙裔美国人和华裔美国人，利用现有的框架NHLBI多种族研究动脉粥样硬化（梅萨）。在目标1中，这项梅萨家族研究将确定非多数美国人群中冠状动脉钙（EBCT和螺旋门控CT扫描）和颈动脉内膜中层厚度（IMT）（B型超声）变异的遗传贡献程度。这将通过使用梅萨研究资源，在Aim 2中对900例梅萨指数病例的1800名同胞进行表型分析来完成（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），并在雪松西奈医学中心和威克森林医学院，将通过基因组扫描方法鉴定与这些定量亚临床心血管疾病特征（冠状动脉钙和IMT）相关的人类基因组中的候选区域。随后将启动这些区域内的定位克隆和候选基因鉴定。在目标3中，我们将进一步追求基因定位和鉴定，通过在基于家族和病例对照的关联研究中测试位置和生物学候选基因。梅萨的目的是评估亚临床CVD并确定多种族人群中的风险因素，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）。与传统的风险因素评估相结合，这种遗传性标志物应该有助于通过有针对性的诊断测试和药理学干预来管理血管疾病患者，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): The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to subclinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT), and to evaluate the impact of lifestyle and environment on the manifestations of these genetic susceptibilities to CVD in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios), evenly distributed among African-Americans, Hispanic-Americans, and Chinese-Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA). In Aim 1, this MESA Family Study will determine the extent of genetic contribution to variation in coronary calcium (EBCT and helical-gated CT scan) and carotid artery intimal-medial thickness (IMT) (B-mode ultrasound) in non-majority U.S. populations. This will be accomplished by phenotyping 1800 siblings of 900 MESA index cases, In Aim 2, using the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers), and bringing to bear the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine, candidate regions in the human genome linked to these quantitative subclinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches. This will be followed by initiation of positional cloning and candidate gene identification within these regions. In Aim 3, we will further pursue gene localization and identification by testing positional and biological candidate genes in both family based and case control association studies. Whereas the purpose of MESA is to assess subclinical CVD and identify 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 subclinical CVD risk factors. In combination with traditional risk factor assessment, such inherited markers should be useful in the management of patients with vascular disease, through targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols, thus resulting in an increase in the overall well-being of the US population.