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了开发新的策略来预防和治疗动脉粥样硬化的必要性。一些证据表明，动脉粥样硬化风险的很大一部分变异性是可遗传的。然而，到目前为止，基于家庭的连锁研究和候选基因分析未能发现导致这种变异的大部分遗传变异。关联研究预计将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对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，使得设计具有出色能力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，再加上NHLBI赞助的几个具有动脉粥样硬化表型详细数据的队列的存在，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一个高度杠杆的机会。当积极的干预措施更有可能阻止疾病的初始发展时，发现这些变异可能会导致早期识别高危对象的新策略。此外，易感于动脉粥样硬化的变异的识别可能会提出新的病理生理途径，作为新的治疗干预的潜在靶点。

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.