MESA Family Study

描述（由申请人提供）：MESA家族研究的总体目标是定位和鉴定导致亚临床心血管疾病（CVD）的基因，通过冠状动脉钙（CAC）和颈动脉内膜内壁厚度（IMT）进行评估，并评估生活方式和环境对美国少数民族CVD遗传易感性表现的影响。利用现有的NHLBI动脉粥样硬化多种族研究（MESA）框架，对来自900个兄弟姐妹（兄弟姐妹）的2700名个体进行研究，这些个体平均分布在非洲裔美国人、西班牙裔美国人和华裔美国人之间。在目的1中，这项MESA家族研究将确定非大多数美国人群冠状动脉钙（EBCT和螺旋门状CT扫描）和颈动脉内膜-内侧厚度（IMT） （b超）变异的遗传贡献程度。在目标2中，利用MESA研究资源（数据协调中心、中央实验室、CT和超声阅读中心、6个临床领域中心），并利用雪松西奈医学中心和维克森林医学院的综合资源和心血管遗传流行病学专业知识，对900个MESA指数病例的1800名兄弟姐妹进行表型分型，从而实现这一目标。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）相关的候选区域将通过基因组扫描方法确定。随后将在这些区域内启动位置克隆和候选基因鉴定。在目标3中，我们将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来进一步追求基因定位和鉴定。MESA的目的是评估亚临床心血管疾病并确定多种族人群中的危险因素，而MESA家族研究的目的是确定导致这些亚临床心血管疾病危险因素的基因（数量性状位点或qtl）。结合传统的风险因素评估，这些遗传标记在血管疾病患者的管理中应该是有用的，通过有针对性的诊断测试和药物干预，并在确定可以从特定预防方案中受益的受试者中，从而增加美国人口的整体福祉。

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.