Causal Relationship between Plasma Amino Acid Metabolites and the Risk of Developing Primary Open-Angle Glaucoma: A Mendelian Randomization Study

BackgroundPrimary open-angle glaucoma (POAG) is a common chronic eye disease with an unknown etiology. Nonetheless, several observational investigations have hinted at a connection between specific plasma amino acid metabolites and primary open-angle glaucoma, yet elucidating the causal link remains challenging.Methods Genetic variables were analyzed using publicly available gene locus data (sample size of 216,275, ncase=16,677, ncontrol=199,580) and the FinnGen Biobank (ncase=34,179, ncontrol=34,932). We used several methods to estimate Mendelian randomization (MR), i.e., MR Egger, weighted median, variance inverse weighting, uncomplicated and scaled models.ResultTwo instrumental variables were employed to evaluate the causal link connecting amino acid levels in plasma metabolites with the likelihood of POAG. The results showed that lysergic acid thiamine (ratio [OR], 0.919; 95% CI, 0.874-0.967; P= 3, using IVW method) and bladder protein (ratio [OR], 0.843; 95% CI, 0.727-0.977; P=2.34e03, Use of the IVW method) exhibited a notable correlation with a reduction in the likelihood of developing POAG.Sensitivity analyses verified the robustness of the results against potential pleiotropic effects.ConclusionThese discoveries offer genetic support for the notion that elevated concentrations of several amino acids in plasma metabolites are linked to a reduced risk of POAG and provide a basis for the clinical diagnosis of POAG at the level of amino acid changes because plasma metabolized amino acid levels affect the structural physiological state and functional properties of retinal neurons, optic nerve fibers, and other ocular cells. Abnormal metabolism can further lead to serious eye diseases such as glaucoma. Given that plasma amino acid metabolite concentrations can be altered by dietary changes or the use of amino acid supplements, our study provides fresh perspectives on possible approaches for the prevention and treatment of POAG.