Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population

PURPOSE: A meta-analysis suggests a relationship be-tween abnormal glucose metabolism and primary open -angle glaucoma (POAG); however, the causal associa-tion between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to as - sess the causal association between genetically predicted glycemic traits and the risk of POAG.center dot DESIGN: Two-sample MR design.center dot METHODS: We examined the genetically predicted mea-sures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP) -exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n = 1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP -outcome association. center dot RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance -weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fast-ing glucose (per 10 mg/dL-increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitiv-ity analyses, including MR -Egger and weighted-median methods, did not support this association ( P > .10).center dot CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population. (Am J Ophthalmol 2023;245: 193-201. (c) 2022 Else-vier Inc. All rights reserved.)