State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
Exp Eye Res. 2024 Sep;246:110000. doi: 10.1016/j.exer.2024.110000. Epub 2024 Jul 9.
Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.
青光眼是全球导致不可逆性失明的主要原因。先前的观察性研究表明，中央角膜厚度（CCT）与青光眼之间存在关联；然而，结果并不一致。本研究旨在探讨 CCT 是否与开角型青光眼（OAG）的发病风险相关。我们采用两样本 Mendelian 随机化方法评估 CCT 与 OAG（即原发性开角型青光眼（POAG）和疑似青光眼）之间的关系。全基因组关联研究中与 CCT 相关的遗传变异作为遗传工具，这些遗传变异在 Iglesias 等人的研究中达到全基因组显著关联（P<5×10），Bonnemaijer 等人的研究中进行了复制。这些工具针对 OAG 的汇总统计数据来自 FinnGen 项目（第 10 版）。遗传易感性的逆方差加权回归表明，CCT 增加与 POAG（比值比 [OR]，1.005；95%置信区间 [CI]，1.002-1.008；P=0.001）和疑似青光眼（OR，1.006；95% CI，1.003-1.009；P<0.001）风险增加呈正相关。在 CCT 的复制样本中，CCT 增加也与 POAG（OR，1.004；95% CI，1.000-1.008；P=0.029）和疑似青光眼（OR，1.005；95% CI，1.001-1.008；P=0.013）风险增加呈正相关。我们发现了支持 CCT 增加与 POAG 和疑似青光眼风险之间存在潜在因果关联的遗传证据，这一结果表明 CCT 在青光眼的诊断和治疗中具有重要的临床意义。需要进一步的研究来阐明这种因果关系的潜在机制。
