Rheumatoid arthritis and diabetic retinopathy: A two-sample Mendelian randomization study

Abstract

Diabetic retinopathy (DR) is a common and highly blinding disease. Many clinical studies have shown a causal relationship between Rheumatoid arthritis (RA) and DR, but the results are contradictory. In addition, some clinical results and pathological inferences have certain paradoxes, and the influence of RA on the pathogenesis and development of DR Is unclear. Our research assessed the causal association between RA and the development of DR using a 2-sample Mendelian randomization method. Single nucleotide polymorphisms (SNPs) relevant to the study were extracted and filtered from genome-wide association study (GWAS) data. A DR GWAS with a sample size of 190,594 and an RA GWAS with a sample size of 58,284 were obtained. Inverse variance weighted (IVW) method was used to analyze the results, and Mendelian randomization (MR)-Egger regression method and weighted median method were used to evaluate the robustness. Sensitivity analysis was performed using pleiotropy test, heterogeneity test, leave-one-out test to ensure that the results were unbiased. Confounding factors were eliminated to ensure robustness. A total of 83 related SNPs were screened. IVW method showed a positive correlation between RA and the increased relative risk of diabetic retinopathy (OR = 1.06, 95%CI: 1.04–1.23). The same trend was shown by MR-Egger regression method and weighted median method. Sensitivity analysis showed that there was no heterogeneity in SNPs, and the results were less likely to be affected by potential bias. After removing SNPs linked to confounders, the MR results remained significant and stable in direction. There is a positive causal association between rheumatoid arthritis and diabetic retinopathy. It is important to strengthen retina-related screening and prevention in diabetic patients with RA to reduce the risk of DR In RA patients.