Mendelian Randomization Analysis of Glycemic Traits and Myopia

MR analysis between the exposures (adiponectin, BMI, fasting blood glucose, fasting insulin, HbA1c, and proinsulin levels) and myopia was performed using the TwoSampleMR v0.5.5 R package (R Foundation for Statistical Computing, Vienna, Austria).²² (link) The following standards were applied in the selection of genetic instruments for each glycemic trait: (1) P < 5 × 10⁻⁸ for each glycemic trait; (2) linkage disequilibrium r2 < 0.001; and (3) linkage disequilibrium distance > 10,000 kb. In this study, the inverse-variance weighted (IVW) method²³ (link) was the main method used to estimate associations between glycemic traits and myopia. For sensitivity analysis, three additional approaches based on the TwoSampleMR R package were used, including MR-Egger regression,²⁴ (link) weighted median method,²⁵ (link) and weighted mode method,²² (link) which allowed for the presence of horizontal pleiotropy. Therefore, MR results were considered meaningful if the IVW method identified an association (P < 0.0083) and all four MR methods had effects in the same direction.
To further assess the robustness of these identified associations, the impact was assessed for potential horizontal pleiotropy; comprehensive sensitivity using the MR pleiotropy residual sum and outlier (MR-PRESSO) test,²⁶ (link) Egger intercept calculation,²⁴ (link) leave-one-out analysis,²² (link) heterogeneity tests,²⁷ (link) and the Steiger test.²⁸ (link)