Department of Ophthalmology, King's College London, London SE5 9RS, United Kingdom.
Department of Twin Research & Genetic Epidemiology, King's College London, London SE5 9RS, United Kingdom.
Annu Rev Vis Sci. 2021 Sep 15;7:727-746. doi: 10.1146/annurev-vision-031021-095225. Epub 2021 Jun 1.
Intraocular pressure (IOP) is the cardinal and only modifiable risk factor for glaucoma, the leading cause of irreparable blindness worldwide. Twin and family studies estimate the heritability of IOP to be 40-70%, and linkage studies for IOP have identified numerous loci. Mutations in can cause markedly elevated IOP and aggressive glaucoma often requiring surgical intervention. However, the majority of the genetic basis for raised IOP and glaucoma in populations is complex, and recent large genome-wide association studies (GWASs) have identified over 100 common variants that contribute to IOP variation. In combination, these loci are predictive for primary open-angle glaucoma in independent populations, achieving an area under the receiver operating characteristic curve of 76% for high-pressure primary open-angle glaucoma; this suggests the possibility of targeted screening in the future. Additionally, GWAS findings have identified important biological pathways underlying IOP regulation, including lymphangiogenesis and lipid metabolism, providing novel targets for new therapies.
眼压（IOP）是青光眼的主要且唯一可改变的危险因素，是全球致盲的主要原因。双胞胎和家族研究估计 IOP 的遗传率为 40-70%，并且对 IOP 的连锁研究已经确定了许多基因座。CAN基因突变可导致明显的IOP升高和侵袭性青光眼，通常需要手术干预。然而，人群中升高的 IOP 和青光眼的遗传基础大部分是复杂的，最近的大型全基因组关联研究（GWAS）已经确定了 100 多个常见变异，这些变异与 IOP 变异有关。这些基因座结合在一起，可以预测原发性开角型青光眼在独立人群中的发生，在高压原发性开角型青光眼的受试者工作特征曲线下面积达到 76%；这表明未来可能进行有针对性的筛查。此外，GWAS 研究结果还确定了眼压调节的重要生物学途径，包括淋巴管生成和脂质代谢，为新疗法提供了新的靶点。
