MESA Family Study

MESA家庭研究

• 批准号: 6891538
• 负责人: KIANG JOHN LIU
• 金额: $ 3.71万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891538
• 关键词: MESA; Family; Study

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.

描述(由申请人提供)：拟议的MESA家族研究的总体目标是通过冠脉钙化(CAC)和颈动脉内膜中膜厚度(IMT)评估，定位和确定亚临床心血管疾病(CVD)的致病基因，并评估生活方式和环境对美国少数族裔人群这些心血管疾病遗传易感性表现的影响。这些目标将在一项针对来自900个兄弟姐妹(兄弟姐妹)的2700人的研究中解决，该研究平均分布在非裔美国人、西班牙裔美国人和华裔美国人中，利用NHLBI动脉粥样硬化多种族研究(MESA)的现有框架。在目标1中，这项MESA家族研究将确定基因对非多数美国人群冠状动脉钙化(EBCT和螺旋门控CT扫描)和颈动脉内中膜厚度(IMT)(B型超声)变化的影响程度。这将通过在目标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个临床现场中心)对900个MESA指数病例的1800个兄弟姐妹进行表型鉴定来实现，并利用锡达斯-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，将通过基因组扫描方法确定人类基因组中与这些量化的亚临床心血管疾病特征(冠状动脉钙质和IMT)相关联的候选区域。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庭和病例对照的关联研究中测试位置和生物候选基因来进一步进行基因定位和鉴定。MESA的目的是评估多民族人群中的亚临床心血管疾病和识别危险因素，而MESA家族研究的目的是识别与这些亚临床心血管疾病危险因素有关的基因(数量性状基因或QTL)。与传统的风险因素评估相结合，这些遗传标记物应该有助于血管疾病患者的管理，通过有针对性的诊断测试和药物干预，以及识别可以从特定预防方案中受益的受试者，从而提高美国人口的整体幸福感。