冠状动脉粥样硬化性心脏病（CHD）和缺血性脑卒中（IS）是遗传和环境因素共同作用的复杂疾病。全基因组关联研究（GWAS）已在中国人群发现和验证了多个CHD遗传易感性区域，而中国人群IS易感性的遗传基础尚未阐明。本课题拟基于已建立的中国慢性病前瞻性研究（CKB）50余万人的超大型队列，应用巢式病例-对照研究设计，开展两阶段多中心IS的GWAS（筛选阶段：2000病例和2000对照；验证阶段：5000病例和5000对照），发现中国人群IS易感区域；针对中国人群GWAS已确定的CHD易感区域进行精细定位研究，通过目标区域定位捕获和高通量测序，以及进一步的关联分析确定各区域遗传标志物及其效应。本课题确定的CHD和IS遗传标志物将为建立相应疾病遗传风险模型提供数据支持，为开展CHD和IS高危人群筛选以及实施目标明确的前期预防提供理论基础和技术支持。

Coronary heart disease (CHD) and ischemic stroke (IS) are caused by a combination of genetic and environmental factors. Genome-wide association studies (GWAS) have identified several susceptibility loci for CHD in Chinese population. However, the genetic determinants of IS in Chinese population are still unclear. Based on an established mega cohort of China Kadoorie Biobank (CKB) with more than 0.5 million subjects, this project will conduct a two-stage GWAS to identify IS related loci using nested case-controls study (screening phase: 2000 cases and 2000 controls; replication phase: 5000 cases and 5000 controls). Furthermore, this project will fine-map the identified regions associated with CHD in Chinese population through target capture and sequencing, and will obtain the genetic markers and estimate their effect sizes for CHD. The identified genetic markers may be used for genetic risk prediction of CHD and IS, which may facilitate to screen high risk population and to perform target population prevention for CHD and IS.