原发性开角型青光眼（POAG）是一种具有遗传异质性的多基因遗传的常见眼病，近年来广泛开展的全基因组关联分析研究（GWAS）在青光眼遗传学领域虽然取得了巨大的成功，找到很多与原发性开角型青光眼相关联的单核苷酸多态性（SNP）及其位于同一区域的候选基因，但这些SNP与疾病的关联强度都比较弱，仅能解释一小部分的遗传因素，且大多数SNP并不位于候选基因的编码区，对基因功能的影响不得而知。越来越多的遗传学证据提示，相对低频率的基因功能性变异也可以是常见疾病的重要遗传机制，本研究拟从常见疾病-罕见变异（CD-RV）的理论角度出发，使用第二代测序（NGS）的方法，以现有的GWAS研究得到的27个与POAG关联的候选基因位点为目标区域，捕获后进行高通量的测序，寻找直接导致基因功能改变的低频率变异，并通过大样本的病例对照验证以及基因型-表型分析，明确POAG的易感基因，为其发病机制的研究提供遗传学的依据。

Primary open angle glaucoma (POAG) is a heterogeneous and multigenic common eye disease. GWASs are very successful in finding POAG associated SNPs and candidate gene loci in recent years. However, the effect sizes of these SNPs are modest and they could only account for a small part of the estimated heritability. Furthermore, most of the associated SNPs are not located within the coding regions of the candidate genes, thus their impacts on gene function are unknown. Increasing genetic evidences support rare variants may play an important role in common diseases as well. Based on the theory of common disease - rare variants, we are going to use the next generation sequence (NGS) method to target 27 POAG candidate loci from GWASs for deep sequencing, in order to detect rare variants which could change gene function directly. Validation with large sample size of case control cohorts and genotype-phenotype analyses will be done in the follow-up. The purpose of this study is to clarify the disease causing genes of POAG and provide genetic evidence to study the pathological mechanism of POAG.