MESA Family Study

MESA家庭研究

• 批准号: 7108581
• 负责人: KAROL E WATSON
• 金额: $ 6.15万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 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/7108581
• 关键词: Hispanic Americans; angiocardioultrasonography; atherosclerosis; calcium; cardiovascular disorder epidemiology; cardiovascular disorder risk; carotid artery; clinical research; computed axial tomography; coronary artery; family genetics; genetic screening; genetic susceptibility; human subject; linkage mapping; population genetics; quantitative trait loci; siblings

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.

描述（由申请人提供）：这是MESA家庭研究的首次重新提交HL071205。拟议的MESA家族研究的总体目标是定位和确定有助于亚临床心血管疾病（CVD）的基因，该基因在美国少数群体中通过冠状动脉钙（CAC）和颈动脉内膜内侧壁厚（IMT）评估。这些目标将在对非裔美国人和西班牙裔美国人之间均匀分布的2700名个人（Sibtrios或更大）的2700个人进行研究，利用了NHLBI多种族研究的动脉粥样硬化研究（MESA）。在AIM 1中，MESA家族研究将确定这两个人群中CAC（EBCT和螺旋门控扫描）和IMT（B模式超声）变异的遗传贡献程度。这个目标将通过检查（表型）的1800个梅萨指数案例（非裔美国人和西班牙裔美国人之间的均匀分裂）来实现。在AIM 2中，将通过基因组扫描方法（包括最佳区域的精细映射）来鉴定与这些定量的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生物候选区域。该目标将使用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），以及在Cedars-Sinai Medical Center和Wake-Forest医学院的合并资源和心血管遗传流行病学专业知识。在AIM 3中，基因定位和鉴定将通过对3个少数MESA（非裔美国人，西班牙裔美国人和中国裔美国人）的受试者的位置和生物候选基因的关联研究来实现。尽管MESA（父母研究）的目的是评估次临床CVD并确定多种族人群中流行病学风险因素，但MESA家族研究的目的是识别有助于这些临界CVD危险因素的基因（定量性状特性或QTL）。结合传统的风险因素评估，确定的遗传标记应在血管疾病患者的管理中有用。这些结果将允许有针对性的诊断测试和药理干预，并在鉴定可以从特定的预防方案中受益的受试者，从而导致美国人口的整体福祉增加。