Glaucoma, a diverse group of eye disorders that results in the degeneration of retinal ganglion cells, is the world's leading cause of irreversible blindness. Apart from age and ancestry, the major risk factor for glaucoma is increased intraocular pressure (IOP). In primary open-angle glaucoma (POAG), the anterior chamber angle is open but there is resistance to aqueous outflow. In primary angle-closure glaucoma (PACG), crowding of the anterior chamber angle due to anatomical alterations impede aqueous drainage through the angle. In exfoliation syndrome and exfoliation glaucoma, deposition of white flaky material throughout the anterior chamber directly interfere with aqueous outflow.

Observational studies have established that there is a strong hereditable component for glaucoma onset and progression. Indeed, a succession of genome wide association studies (GWAS) that were centered upon single nucleotide polymorphisms (SNP) have yielded more than a hundred genetic markers associated with glaucoma risk. However, a shortcoming of GWAS studies is the difficulty in identifying the actual effector genes responsible for disease pathogenesis. Building on the foundation laid by GWAS studies, research groups have recently begun to perform whole exome-sequencing to evaluate the contribution of protein-changing, coding sequence genetic variants to glaucoma risk. The adoption of this technology in both large population-based studies as well as family studies are revealing the presence of novel, protein-changing genetic variants that could enrich our understanding of the pathogenesis of glaucoma.

This review will cover recent advances in the genetics of primary open-angle glaucoma, primary angle-closure glaucoma and exfoliation glaucoma, which collectively make up the vast majority of all glaucoma cases in the world today. We will discuss how recent advances in research methodology have uncovered new risk genes, and how follow up biological investigations could be undertaken in order to define how the risk encoded by a genetic sequence variant comes into play in patients. We will also hypothesise how data arising from characterising these genetic variants could be utilized to predict glaucoma risk and the manner in which new therapeutic strategies might be informed.

青光眼是导致视网膜神经节细胞退化的多种眼部疾病，是世界上导致不可逆失明的主要原因。除年龄和血统外，青光眼的主要危险因素是眼压（IOP）升高。在原发性开角型青光眼 (POAG) 中，前房角是开放的，但对房水流出有阻力。在原发性闭角型青光眼 (PACG) 中，由于解剖学改变导致的前房角拥挤会阻碍房水通过前房角引流。在剥脱综合征和剥脱性青光眼中，整个前房中白色片状物质的沉积直接干扰房水流出。

观察性研究已经确定，青光眼的发病和进展有很强的可遗传因素。事实上，一系列以单核苷酸多态性 (SNP) 为中心的全基因组关联研究 (GWAS) 已经产生了一百多个与青光眼风险相关的遗传标记。然而，GWAS 研究的一个缺点是难以确定负责疾病发病机制的实际效应基因。在 GWAS 研究奠定的基础上，研究小组最近开始进行全外显子组测序，以评估蛋白质改变、编码序列遗传变异对青光眼风险的贡献。这项技术在大型人群研究和家庭研究中的采用都揭示了新奇的存在，

这篇综述将涵盖原发性开角型青光眼、原发性闭角型青光眼和剥脱性青光眼的遗传学最新进展，它们共同构成了当今世界上绝大多数青光眼病例。我们将讨论研究方法的最新进展如何发现新的风险基因，以及如何进行后续生物学研究以确定基因序列变异编码的风险如何在患者中发挥作用。我们还将假设如何利用表征这些遗传变异的数据来预测青光眼风险以及可能告知新治疗策略的方式。