SNPs and Extent of Atherosclerosis (SEA) Study

The SEA study is a genome-wide association study to identify genetic variants associated with premature atherosclerosis in subjects included in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) repository - a unique NHLBI resource including data, DNA and arterial specimens from over 3000 multi-ethnic subjects 15-34 years of age who died of non-atherosclerotic causes (mostly trauma). All PDAY subjects had post-mortem quantitative assessment of raised atherosclerotic lesions in their aorta and coronary arteries - making this the largest and most carefully phenotyped cohort for premature atherosclerosis in the world. The goal of the current project was to use the quantitative measure of raised atherosclerotic lesions in the PDAY cohort as the target phenotype for a genome-wide association study and to use quantitative measures of subclinical atherosclerosis (coronary calcium and carotid IMT) in the Multi-Ethnic Study of Atherosclerosis (MESA) to confirm or refute candidate loci identified from the PDAY analysis. Identifying genetic factors that predispose individuals to premature atherosclerosis could lead to more effective screening and early treatment of high risk individuals and suggest novel molecular targets for treatment and prevention interventions.

SEA研究是一项全基因组关联研究（genome-wide association study），旨在从青年动脉粥样硬化病理生物学决定因素（Pathobiological Determinants of Atherosclerosis in Youth, PDAY）数据库收录的受试者中，筛选与早发性动脉粥样硬化相关的遗传变异。PDAY数据库是美国国立心肺血液研究所（National Heart, Lung, and Blood Institute, NHLBI）独有的生物资源，收纳了超过3000名15~34岁、因非动脉粥样硬化性病因（多为创伤）死亡的多种族受试者的数据、脱氧核糖核酸（Deoxyribonucleic Acid, DNA）及动脉标本。

所有PDAY受试者均接受了死后主动脉与冠状动脉粥样硬化隆起性病变的定量评估，使其成为全球规模最大、表型分型最严谨的早发性动脉粥样硬化队列。

本项目的研究目标为：以PDAY队列中粥样硬化隆起性病变的定量检测结果作为全基因组关联研究的靶表型，并利用多民族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA）中的亚临床动脉粥样硬化定量检测数据——包括冠状动脉钙化（coronary calcium）与颈动脉内膜中层厚度（carotid IMT）——验证或推翻从PDAY分析中筛选出的候选基因座。

识别促使个体罹患早发性动脉粥样硬化的遗传因素，有望为高危人群提供更有效的筛查与早期治疗策略，并为治疗与预防干预措施提供全新的分子靶点。