SNPs and Extent of Atherosclerosis (SEA) Study

描述（由申请人提供）：心血管疾病的持续负担强调需要制定新的策略来预防和治疗动脉粥样硬化。多项证据表明，动脉粥样硬化风险的很大一部分可变性是遗传的。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导致这种变异的遗传变异。据预测，在检测导致常见复杂表型（如动脉粥样硬化）的遗传变异方面，关联研究比连锁研究更有效。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是不切实际的。最近，这些限制已经被克服，使得能够设计出具有出色能力的关联研究，以检测导致疾病风险的常见变异。这些技术的发展，结合NHLBI赞助的几个具有动脉粥样硬化详细表型数据的队列的存在，为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提供了高度杠杆的机会。当积极的干预更有可能预防疾病的最初发展时，发现这些变异可能会导致早期识别高风险受试者的新策略。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，可以作为新的治疗干预措施的潜在靶点进行探索。

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.