To investigate the association between blood and urine biomarkers and genetic risks of primary glaucoma using Mendelian randomization analysis.

This study utilized summary data from large - scale genome-wide association studies to extract eligible instrumental variables and primarily employed the inverse variance weighted (IVW) method for analysis. The results were validated through Cochran’s Q statistic, MR - Egger regression intercept, MR - PRESSO, and the leave - one - out method.

MR analysis showed that the total protein (IVW: OR=1.399, 95% CI: 1.000-1.958, P=0.049), glycated hemoglobin (IVW: OR=0.650, 95% CI: 0.512-0.824, P<0.001), and glucose (IVW: OR=0.587, 95% CI: 0.368-0.938, P=0.026) were causally related to primary glaucoma. Reverse MR analysis further found a causal relationship between primary angle - closure glaucoma and total protein (IVW: OR=0.990, 95% CI: 0.980-0.999, P=0.045), indicating a bidirectional causal relationship between total protein and primary angle - closure glaucoma. The results were validated without finding heterogeneity or horizontal pleiotropy.

Total protein may be a potential risk factor for primary angle - closure glaucoma, while glycated hemoglobin and glucose may serve as protective factors against primary open -angle glaucoma. Total protein and albumin are potential biomarkers for primary angle -closure glaucoma. This study provides information on biomarkers that can be further investigated, offering new insights and strategies for the early diagnosis, personalized treatment, and prevention of glaucoma.