[Association between type 2 diabetes mellitus and the risk of developing cataracts: based on the research of two-sample Mendelian randomization].

Abstract

Objective: To determine the causal relationship between cataracts and type 2 diabetes mellitus (T2D) by the Mendelian randomization (MR) analysis using the genome-wide association study (GWAS) data. Methods: Data on T2D and cataracts in the European population were obtained from the OpenGWAS database. The single nucleotide polymorphisms (SNPs) that met the genome-wide significance criteria (P<5×10⁻⁸) of T2D (48 286 cases, 250 671 controls) and cataracts (5 045 cases, 356 096 controls) were selected. The main method was random effects inverse variance weighting (IVW), and four other two-sample MR methods were also used, including MR Egger, Simple median, Weighted median, and Weighted mode, to assess the causal relationship using odds ratios (OR). Sensitivity analyses were conducted using the leave-one-out approach to evaluate the robustness of the results. Results: The MR Egger analysis showed a significant risk association between T2D and cataracts (OR=1.003, 95%CI=1.001-1.006; P=0.013). Using the methods of Weighted median (OR=1.002, 95%CI=1.000-1.004; P=0.029) and Weighted mode (OR=1.002, 95%CI=1.000-1.005; P=0.046), similar results were obtained. However, the IVW test failed to confirm the causality (P=0.149). The sensitivity analyses using the MR Egger and IVW tests did not show significant heterogeneity between T2D and cataracts (all P>0.05). With the leave-one-out analysis, the SNPs with significant effects were not identified, indicating the robustness of the MR results in this study. The MR Egger interception of the SNPs showed significant directional pleiotropy (P=0.038), suggesting a directional pleiotropy between T2D and cataracts. Conclusions: The results of the MR analysis suggest there is a causal relationship between T2D and cataracts, and T2D increases the risk of cataracts.