IGF::OT::IGF R&D- MEDICAL: BIOMEDICAL (APPLIED RESEARCH/EXPLORATORY DEVELOPMENT)

承包商将利用现有的庞大而独特的妇女健康倡议生物资源，其中包括来自大量绝经后妇女的生物血库，这些妇女在长达19年的随访期间进行了广泛的表型分析。承包商将仔细分析冠心病（CHD）病例（n ~1070）的DNA和血浆，以及一组适当的对照（n =~1070），在基线时使用两种互补但经过充分验证的基因组技术。这些高通量基因组技术有望产生高质量和高分辨率的全基因组DNA甲基化谱，以及对血浆中循环microRNA水平的全面评估。然后，承包商将使用由调查小组成员开发的最先进的统计方法，将这些基因组数据与现有的临床、遗传和生物标记数据进行全面分析和整合，以确定与冠心病及其风险因素相关的基因组特征和途径。

The contractor will take advantage of the existing large and unique Women's Health Initiative biological resource, which includes bio-banked blood from a large number of postmenopausal women who have been extensively phenotyped over a follow up period of up to 19 years. The contractor will carefully profile the DNA and plasma of coronary heart disease (CHD) cases (n ~ 1070), as well as an appropriate set of controls (n =~1070), using two complementary, but well-validated, genomic technologies at baseline. These high throughput genomic technologies are expected to generate high quality and high-resolution genome wide DNA methylation profiles as well as a comprehensive assessment of circulating microRNA levels in plasma. The contractor will then comprehensively analyze and integrate this genomic data with existing clinical, genetic, and biomarker data using state of the art statistical methodologies developed by members of the investigative team to identify genomic signatures and pathways relevant to CHD and its risk factors.