高血压是一个全球性的重要公共卫生问题，其患病率呈增长态势。中国人群血压全基因组关联研究发现了18个相关位点，但相关遗传变异及关键分泌蛋白与高血压发病的关系尚未明确，因此有必要开展深入研究以发现新的高血压危险因素。本项目拟在已建立的高血压队列基础上，开展具有较好的成本-效益关系的多阶段研究。首先，在极端高血压病例和对照样本中，对中国人群报道的重要血压相关基因的功能区域进行高通量测序，筛选与高血压相关的功能性变异位点，并在大样本中验证新的功能性变异与高血压的关联；其次，在队列样本中分析新发现的功能性变异与高血压发病的关系，同时对基因所调控的关键分泌蛋白进行血清学检测，分析其与高血压发病的关系。本研究将为高血压发病机制研究提供重要的流行病学数据，为高血压预防策略的制定及新药开发提供新思路。

Hypertension is a major public health problem worldwide, of which the prevalence is increasing. A genome-wide association study in the Chinese Han population has identified 18 blood pressure-associated loci. However, the relationships of functional variants and key secretory protein levels with hypertension incidence are still unclear. Hence, there is a great need to carry out further studies to explore these relationships and discover new risk factors for hypertension. Based on the established prospective cohort of hypertension, we design a good cost-benefit multi-stage study. Firstly, in extreme hypertensive cases and controls, high-throughput sequencing technique will be used to detect blood pressure-associated functional variants in the 18 genomic regions, following by verification in a large case-control sample. Secondly, the relationship between the newly detected functional variations and incident hypertension, as well as the relationship between serum levels of key secretory proteins and incident hypertension will be evaluated in a hypertension cohort. This project will provide important epidemic data for the research of the pathogenesis of hypertension, and new idea on developing novel drugs and prevention strategies for hypertension.