Abstract：
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 × 10-8) 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.
摘要：
青光眼是全球不可逆失明的主要原因。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系；然而，结果不一致。这项研究旨在调查CCT是否与发生开角型青光眼（OAG）的风险有关。我们采用双样本孟德尔随机化来评估CCT和OAG之间的关系，即,原发性开角型青光眼（POAG）和疑似青光眼。从Iglesias等人发表的全基因组关联研究中获得了由与全基因组意义上的CCT相关的变体组成的遗传仪器(P<5×10-8)。发现和Bonnemaijer等人。用于复制。从FinnGen项目（第10版）获得了OAG的这些工具的摘要级统计数据。遗传易感性的逆方差加权回归预测CCT增加与POAG风险增加正相关(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）。在CCT的复制样本中，CCT升高也与POAG风险增加呈正相关(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）。我们发现遗传证据支持欧洲人群中CCT升高与POAG和疑似青光眼风险之间的潜在因果关系。这一发现表明CCT在青光眼诊断和治疗中的临床意义。需要进一步的研究来阐明这种因果关系的潜在机制。
