最近国际上开展的心血管疾病全基因组关联研究（GWAS），包括申请者在中国人群中开展的冠心病、血压和血脂GWAS，确定了一系列心血管疾病遗传易感基因和位点。本研究将全面整合影响中国人群冠心病、血压和血脂的遗传易感因素，在大规模病例对照和高危人群中，识别引起血脂升高进而致冠心病发病风险增加的易感位点；进而在前瞻队列人群中评估所有心血管疾病相关易感因素在心血管疾病发病和死亡中的作用，寻找风险预警和疾病分层的关键遗传标志物，最后综合遗传风险评分和环境危险因素构建心血管疾病发病风险预测模型，以实现基础研究到临床和预防应用的转化。

Recent genome-wide association studies (GWAS) of cardiovascular diseases（CVD）, including GWAS studies in Chinese carried out by us, have discovered multiple genetic loci associated with cardiovascular diseases. However, genetic effect on risk of incident cardiovascular disease is uncertain, particularly among Chinese who may have different genetic and environmental exposures from Europeans. For this study, based on the results of GWAS of cardiovascular diseases in Chinese and Europeans, we aim to assess the impact of genetic variants that have been shown to associate with traditional risk factors on coronary artery disease (CAD) in CAD cases and controls. Then we will examine the association between genetic predisposition to CVD and risk of incident cardiovascular disease inpopulation-based prospective cohorts to identify the key genetic predictors, and then evaluate the predictive value of genetic and environmental factors for the incidence of cardiovascular disease. This study will allow us comprehensively understand the genetic basis of CVD and accelerate progress in translating disease genetics into potential clinical and preventive utility.

本项目主要通过外显子组研究策略，在4.7 万东亚人群和2.8 万例中国人群（9,661冠心病病例和18,558 对照）中系统鉴定了我国人群血脂紊乱和冠心病功能遗传变异，并识别引起血脂升高进而致冠心病发病风险增加的易感基因和位点。在国际上首次鉴定出12 个影响血脂的易感基因和一个新的冠心病易感基因MCU 以及一系列影响中国人群冠心病发生的功能变异位点。本研究揭示了心血管病相关的低频和罕见变异呈现出普遍的种族特异性，将有助于推动冠心病和血脂紊乱的遗传分子机制的解析，促进心血管病高危人群的识别和预测及新的药物靶点的揭示，具有重要临床和预防转化应用价值。发表SCI 论文1 篇（Nature Genetics），申报1项专利，获教育部高等院校自然科学奖二等奖。