Genetic Epidemiology of CVD Risk Factors

CVD危险因素的遗传流行病学

• 批准号: 6992741
• 负责人: SHELLEY A COLE
• 金额: $ 42.04万
• 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 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992741
• 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

DESCRIPTION (provided by applicant): 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, multigenerational, 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 kindred's 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.

描述（由申请人提供）：了解常见多因素疾病（如心血管疾病（CVD））的遗传基础仍然是一个难以捉摸的目标，但近年来分子遗传技术、统计遗传学方法和CVD风险因素表型评估的巨大进步促进了对心脏病风险的更复杂遗传学研究。本研究的总体目标是阐明影响CVD风险因素的遗传因素的作用，最终确定影响CVD风险年龄相关进展的特定基因。这一目标将通过一个新的和创新的合作研究项目，包括协调R 01赠款赖特州立大学医学院和西南生物医学研究基金会追求。这项研究的人群集中在五个大的，多代的，大家庭（四个白色和一个非洲裔美国人）的764个人，最初是在25年前进行的。从原始参与者那里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。然而，在某种程度上，最初的研究是超前的，因为成本效益高的全基因组作图和统计遗传学方法用于有效分析来自大家族的家族数据还需要一二十年。 这项研究包括四个具体目标：1）从大约500名原始参与者那里收集25年的随访数据，并从大约500名未在原始研究中检查的亲属那里收集新数据。收集的CVD危险因素表型包括血流动力学指标、颈动脉内膜中层厚度和心肺功能指标。2)从这1,000个个体中获取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)使用适合于大家庭亲属的横断面和系列（随访）数据的定量遗传学方法，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，以确定染色体区域（QTL）窝藏基因，影响个体变异的CVD危险因素。在这些连锁分析之后，我们将用精细作图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。