冠心病和缺血性脑卒中已经成为威胁我国人群健康的两种重要的动脉粥样硬化性心脑血管疾病。环境和遗传因素及其复杂的交互作用如何影响这两种疾病的发生仍不完全清楚，且已有的证据多来自西方发达国家人群，并不完全适用于中国人群。本项目以已建立的中国慢性病前瞻性研究项目超大型人群队列为基础：描述我国这两种疾病及其主要危险因素的长期变化趋势；分析生物学、行为、心理、社会等危险因素及特殊暴露对两种疾病发生的单独和联合作用；筛选和验证中国人群中两种疾病的遗传易感位点（区域）；探讨DNA甲基化水平及其变化趋势与冠心病间的联系；进一步分析遗传与环境因素复杂的交互作用对两种疾病发生的作用，在此基础上，尝试构建和评价适用于中国人群的两种疾病发生风险的预测模型。本项目将为制定我国冠心病和缺血性脑卒中的防治对策、更新相关疾病防治指南、更有效的识别高危人群提供中国人群高质量的病因学证据。

Coronary heart disease (CHD) and ischemic stroke (IS) have become two major atherosclerotic cardiovascular diseases that threaten the health of the population in China. The environmental and genetic factors and their interactions in the etiology of CHD and IS has not been well understood, and current best available evidence is obtained mostly in populations of Western developed countries. The proposed research is based on the China Kadoorie Biobank (CKB), an extremely large-scale prospective cohort study which is unique in the world. The aims of the proposed study include describing the secular trends of longitudinal changes in morbidity and mortality of CHD and IS and their major risk factors; analyzing independent effect and complex interactive effect of various traditional-known and novel-unknown biological, behavioral, psychological and sociological risk factors and adverse environmental exposures on the disease risk of CHD and IS of Chinese population; screening and validating genetic variants associated with CHD and IS in Chinese population; exploring association of CHD with genome-wide and gene-specific DNA methylation and the longitudinal changes of DNA methylation; analyzing complex interactive effect of environmental and genetic factors on CHD and IS, and exploring feasibility of establishing and evaluating risk predictions models for CHD and IS. The findings of the proposed research will provide high-quality etiological evidence for developing nation-wide preventive strategies and measures, timely updating prevention and treatment guidelines, and screening effectively high-risk population in China.