Glaucoma is a leading cause of irreversible blindness worldwide, with its pathogenesis incompletely understood. Inflammation, as an important aspect of glaucoma, has attracted increasing attention. In this study, we performed a Mendelian randomization (MR) analysis to investigate the association between 91 circulating inflammatory proteins and glaucoma. First, a bidirectional MR was employed to screen for inflammatory proteins that potentially influence glaucoma risk, with the findings further confirmed by a replication sample MR. Then, a mediation analysis was employed to assess the mediating effects of glaucoma endophenotypes on glaucoma. Finally, we performed a subgroup MR to investigate the association between circulating proteins and glaucoma subtypes, including primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). The bidirectional MR suggested 7 out of the 91 proteins were possibly related with glaucoma risk, with T-cell surface glycoprotein CD5 (CD5) (odds ratio (OR) = 0.87
95% confidence interval (CI): 0.81-0.94
P = 2.46 × 10