Causal relationship between central corneal thickness and open-angle glaucoma: Evidence from Mendelian randomization

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 x 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-varianceweighted 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.