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<p>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; <i>P</i> = 2.46 × 10<sup>−4</sup>) 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; <i>P</i> = 1.56 × 10<sup>−3</sup>) 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.</p>

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Association between 91 circulating inflammatory proteins and the risk of glaucoma: A Mendelian randomization study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月14日

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  • Weichen Xu,
  • Qinglu Fan,
  • Yang Meng,
  • Zhihao Nie,
  • Abdulla Sawut,
  • Songping Xie,
  • Changzheng Chen

摘要

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 × 10−4) 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 × 10−3) 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.