Causal association between 91 circulating inflammatory proteins and primary open-angle glaucoma: a bidirectional...

Area of Science:

• Ophthalmology
• Genetics
• Immunology

Background:

• Primary open-angle glaucoma (POAG) is a major cause of irreversible vision loss.
• While elevated intraocular pressure is a key risk factor, POAG pathogenesis also involves inflammation.
• The precise role of systemic inflammation in POAG requires further investigation.

Purpose of the Study:

• To investigate the causal relationships between circulating inflammatory proteins and POAG.
• To utilize a bidirectional Mendelian randomization (MR) approach for robust analysis.
• To identify potential therapeutic targets for POAG prevention and management.

Main Methods:

• A bidirectional two-sample MR analysis was performed using genome-wide association study summary statistics.
• The study included a primary analysis of 91 circulating inflammatory proteins and a replication stage for significant findings.
• Random-effects inverse-variance weighted models and multivariable MR were employed, alongside sensitivity analyses.

Main Results:

• Nine circulating inflammatory proteins showed significant causal effects on POAG risk.
• Higher levels of DNER, LIF, MMP-10, and SCF were positively associated with POAG risk.
• Lower levels of FGF-19, IL-18, IL-18R1, TNFSF14, and TRANCE were inversely associated with POAG risk.
• Replication confirmed associations for FGF-19, IL-18, IL-18R1, and LIF.

Conclusions:

• This study identified causal links between specific inflammatory proteins and POAG.
• FGF-19, IL-18, IL-18R1, and LIF are highlighted as potential therapeutic targets.
• Findings offer new insights into POAG prevention and management, warranting further mechanistic studies.