MESA Family Study

MESA家庭研究

• 批准号: 7255531
• 负责人: KIANG JOHN LIU
• 金额: $ 6.87万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255531
• 关键词: Address; African American; Atherosclerosis; Biological; Calcium; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Chinese American; Chromosome Mapping; Clinical; Coronary; Data Coordinating Center; Diagnostic tests; Family Study; Genes; Genetic; Genome Scan; Goals; Hispanic Americans; Human Genome; Individual; Inherited; Intervention; Laboratories; Link; Maps; Medial; Medical center; Minority; Parents; Patients; Personal Satisfaction; Phenotype; Population; Prevention Protocols; Purpose; Quantitative Trait Loci; Reading; Resources; Risk Factors; Siblings; Thick; Ultrasonography; Variant; Vascular Diseases; X-Ray Computed Tomography; cardiovascular disorder risk; forest; genetic epidemiology; indexing; medical schools; trait

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 HL071205 的首次重新提交。拟议的 MESA 家族研究的总体目标是通过美国少数族群的冠状动脉钙 (CAC) 和颈动脉内膜内壁厚度 (IMT) 进行评估，定位和识别导致亚临床心血管疾病 (CVD) 的基因。这些目标将在一项针对来自 900 个同胞（sibtrios 或更大）的 2700 名个体的研究中得到实现，这些个体均匀分布在非裔美国人和西班牙裔美国人中，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，MESA 家族研究将确定遗传对这两个人群中 CAC（EBCT 和螺旋门控 CT 扫描）和 IMT（B 型超声）变异的影响程度。这一目标将通过对来自 900 个 MESA 索引病例（非洲裔美国人和西班牙裔美国人各占一半）的 1800 名兄弟姐妹进行检查（表型分析）来实现。在目标 2 中，将通过基因组扫描方法识别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，包括最佳区域的精细绘图。这一目标将利用 MESA 研究资源（数据协调中心、中心实验室、CT 和超声读取中心、6 个临床现场中心）以及雪松-西奈医疗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。在目标 3 中，基因定位和鉴定将通过对 MESA 3 个少数群体（非裔美国人、西班牙裔美国人和华裔美国人）的受试者的位置和生物学候选基因的关联研究来完成。 MESA（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危险因素，而 MESA 家族研究的目的是确定导致这些亚临床 CVD 危险因素的基因（数量性状位点或 QTL）。与传统的危险因素评估相结合，确定的遗传标记应该有助于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物干预，并确定可以从特定预防方案中受益的受试者，从而提高美国人口的整体福祉。