Genetic Epidemiology of CVD Risk Factors

CVD危险因素的遗传流行病学

• 批准号: 6823216
• 负责人: SHELLEY A COLE
• 金额: $ 54.21万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-20 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6823216
• 关键词: cardiovascular disorder; cardiovascular disorder epidemiology; cardiovascular function; clinical research; family genetics; genetic markers; genetic susceptibility; hemodynamics; high throughput technology; human data; human subject; linkage mapping; longitudinal human study; quantitative trait loci

EXCEED THE SPACE PROVIDED. Understanding the genetic basis of common multifactorial diseases such as cardiovascular disease (CVD) remains an elusive goal, but the great advances in molecular genetic technology, statistical genetic methods, and phenotypic assessment of CVD risk factors in recent years have facilitated more sophisticated genetic studies of risks for heart disease. The overall goal of this study is to elucidate the role of genetic factors influencing risk factors for CVD, ultimately identifying specific genes influencing the age-related progression of CVD risks. This goal will be pursued through a new and innovative collaborative research project consisting of coordinated R01 grants to Wright State University School of Medicine and the Southwest Foundation for Biomedical Research. The study population centers on 764 individuals in five large, multigeneration, extended families (four white and one African-American) originally examined 25 years ago. Data collected from the original participants includes hundreds of biochemical, medical, physiological, behavioral, physical, psychological, genetic and demographic traits. To some extent, though, the original study was ahead of its time in that cost-effective whole genome mapping and statistical genetic methods for effective analysis of familial data from large extended kindreds were a decade or two away. The proposed study consists of four specific aims: 1) Collect 25-year follow-up data from approximately 500 of the original participants, and new data from approximately 500 of their relatives not examined in the original study. The CVD risk factor phenotypes to be collected include hemodynamic measures, carotid intima-media thickness, and measures of cardiopulmonary function. 2) Obtain DNA samples from these 1,000 individuals and use modern high-throughput molecular genotyping methods to create a 10 cM genetic marker map. 3) Quantify and characterize the nature of genetic influences on CVD risk factors using quantitative genetic methods suited for cross-sectional and serial (follow-up) data from relatives in large extended families. 4) Conduct linkage analyses to identify chromosomal regions (QTLs) harboring genes that influence individual variation in CVD risk factors. Following these linkage analyses, we will examine more closely our strongest linkage signals with fine mapping linkage analysis in order to narrow chromosomal regions of interest. Lifespan Health Research Center Department of Community Health Wright State University School of Medicine Kettering, OH 45420 National Human Genome Research Institute Baltimore, MD PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。了解心血管疾病 (CVD) 等常见多因素疾病的遗传基础仍然是一个难以实现的目标，但近年来分子遗传学技术、统计遗传学方法和 CVD 危险因素表型评估的巨大进步促进了对心脏病风险进行更复杂的遗传学研究。本研究的总体目标是阐明遗传因素影响 CVD 风险因素的作用，最终确定影响 CVD 风险与年龄相关进展的特定基因。这一目标将通过一个新的创新合作研究项目来实现，该项目包括向莱特州立大学医学院和西南生物医学研究基金会提供协调的 R01 拨款。该研究人群以 5 个多代大家庭（四名白人和一名非洲裔美国人）中的 764 名个体为中心，最初于 25 年前进行了调查。从原始参与者收集的数据包括数百种生化、医学、生理、行为、身体、心理、遗传和人口特征。不过，在某种程度上，最初的研究是超前的，因为距离大型亲属的家族数据的有效分析具有成本效益的全基因组图谱和统计遗传方法还需要一两年的时间。拟议的研究包括四个具体目标：1）收集约 500 名原始参与者的 25 年随访数据，以及来自约 500 名原始研究中未检查的其亲属的新数据。要收集的CVD危险因素表型包括血流动力学测量、颈动脉内膜中层厚度和心肺功能测量。 2) 从这 1,000 个人中获取 DNA 样本，并使用现代高通量分子基因分型方法创建 10 cM 遗传标记图谱。 3) 使用适合大家庭亲属的横断面和连续（后续）数据的定量遗传方法，量化和表征遗传对 CVD 危险因素的影响的性质。 4) 进行连锁分析，以确定含有影响 CVD 危险因素个体变异的基因的染色体区域 (QTL)。在这些连锁分析之后，我们将通过精细定位连锁分析更仔细地检查我们最强的连锁信号，以缩小感兴趣的染色体区域。寿命健康研究中心 社区健康部 莱特州立大学医学院 Kettering, OH 45420 国家人类基因组研究所 巴尔的摩, MD 性能网站 ============================================ 部分 结束=============================================