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Abstract #126131 Published in IGR 25-2
Association between 91 circulating inflammatory proteins and the risk of glaucoma: A Mendelian randomization study
Xu W; Fan Q; Meng Y; Nie Z; Sawut A; Xie S; Chen CScientific reports 2025; 15: 8876
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) passing false discovery rate correction. This result was verified by the replication sample MR. The mediation analysis revealed that intraocular pressure (IOP) (β=-0.05; 95% CI: -0.02--0.09; P = 1.56 × 10) was a mediator of CD5's protective effect on glaucoma. The subgroup MR indicated that CD5 conferred a protective causal effect specifically on POAG, not PACG. Moreover, IOP served as a mediator in the association between CD5 and POAG, explaining a proportion of 38.29% of CD5's protective effect against POAG. Our findings suggest a negative causal association between circulating CD5 and POAG risk, which is partially mediated by IOP. This indicates that targeted CD5 therapy may be beneficial to POAG eyes.
Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, China.
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