SNPs and Extent of Atherosclerosis (SEA) Study

SNP 和动脉粥样硬化程度 (SEA) 研究

• 批准号: 7035418
• 负责人: DAVID McLeod HERRINGTON
• 金额: $ 235.39万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7035418
• 关键词: African American; Chinese American; Hispanic Americans; adolescence (12-20); adult human (21+); atherosclerosis; atherosclerotic plaque; biotechnology; cardiovascular disorder epidemiology; cardiovascular disorder risk; caucasian American; clinical research; gene environment interaction; gene interaction; genetic screening; genetic susceptibility; genotype; human data; human genetic material tag; human tissue; molecular biology information system; racial /ethnic difference; single nucleotide polymorphism

DESCRIPTION (provided by applicant): The ongoing burden of cardiovascular disease emphasizes the need to develop new strategies to prevent and treat atherosclerosis. Several lines of evidence indicate that a significant portion of variability in risk for atherosclerosis is heritable. However, to date family-based linkage studies and candidate gene analyses have failed to discover genetic variants that account for most of this variation. Association studies are predicted to be more efficient than linkage studies to detect genetic variants that contribute to common complex phenotypes like atherosclerosis. However, in the past, adequate genome-wide association studies have been impractical due to limitations in genotyping capacity and incomplete documentation of the common variants in the human genome. Recently, these limitations have been overcome, making it possible to design association studies with excellent power to detect common variants contributing to disease risk. These technological developments, combined with the existence of several NHLBI sponsored cohorts with detailed phenotypic data on atherosclerosis provide a highly leveraged opportunity to search for genetic variants associated with early and extensive subclinical atherosclerosis. Discovering such variants could lead to new strategies for early identification of high risk subjects when aggressive intervention would be more likely to prevent the initial development of disease. In addition, identification of variants that predispose to atherosclerosis may suggest novel pathophysiologic pathways that could be explored as potential targets for new therapeutic interventions.

描述（由申请人提供）：心血管疾病的持续负担强调了开发预防和治疗动脉粥样硬化的新策略的必要性。几条证据表明动脉粥样硬化风险的变异性中有很大一部分是可遗传的。然而，迄今为止，基于家族的连锁研究和候选基因分析未能发现占这种变异的大部分的遗传变异。预测关联研究比连锁研究更有效地检测导致动脉粥样硬化等常见复杂表型的遗传变异。然而，在过去，由于基因分型能力的限制和人类基因组中常见变异的不完整记录，充分的全基因组关联研究一直是不切实际的。最近，这些局限性已经被克服，使得设计具有出色功效的关联研究来检测导致疾病风险的常见变异成为可能。这些技术的发展，结合存在的几个NHLBI申办的队列动脉粥样硬化的详细表型数据提供了一个高度杠杆的机会，以寻找与早期和广泛的亚临床动脉粥样硬化相关的遗传变异。发现这些变异可能导致早期识别高风险受试者的新策略，而积极的干预更有可能预防疾病的最初发展。此外，鉴定易患动脉粥样硬化的变异可能提示新的病理生理途径，可作为新的治疗干预的潜在靶点进行探索。