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Abstract #105869 Published in IGR 23-3
Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population
Hanyuda A; Goto A; Nakatochi M; Sutoh Y; Narita A; Nakano S; Katagiri R; Wakai K; Takashima N; Koyama T; Arisawa K; Imoto I; Momozawa Y; Tanno K; Shimizu A; Hozawa A; Kinoshita K; Yamaji T; Sawada N; Iwagami M; Yuki K; Tsubota K; Negishi K; Matsuo K; Yamamoto M; Sasaki M; Tsugane S; Iwasaki MAmerican Journal of Ophthalmology 2023; 245: 193-201
PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures 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. 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 fasting 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, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P > .10). CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.
From the Department of Ophthalmology (A.H., K.Y., K.T., K.N.), Keio University School of Medicine, Tokyo, Japan; Division of Epidemiology (A.H., A.G., S.N., R.K., T.Y., M.I., M.I.), National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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