Causal Influence of Immune Factors on the Risk of Diabetic Retinopathy: a Mendelian Randomization Study

Objectives: Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients. Various mechanisms have been implicated in the pathogenesis of DR. Previous studies have observed the relationship between immune factors and DR, but the causal relationship has not been determined.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis of 731 immune cells and DR, using publicly available genome-wide association study (GWAS) summary statistics, to evaluate potential causal relationships between them. Four types of immune traits were included in the analysis through flow cytometry. GWAS statistics for DR were obtained from the Finngen database, which performed GWAS on 190,594 European individuals (Ncase = 14,584, Ncontrol = 176,010) to assess genetically predicted DR. The primary method used to perform causality analysis was inverse variance weighting (IVW).

Results: Following false discovery rate (FDR) correction, 11MFI-DR, 5AC-DR, 5RC-DR, and 1MP-DR reached a significant causal association level (P < 0.05). Notably, all AC traits exhibited potential associations with a decreased risk of DR(OR < 1), while a majority of MFI traits, along with the singular MP trait, exhibited potential associations with an increased risk of DR (OR > 1). The highest proportion of T-cell subsets in the final results.

Conclusion: This study elucidates that the progression of DR is intricately influenced by immune responses, thereby confirming the immunological susceptibility of DR. Our findings may offer new targets for diagnosing and treating DR, as well as aid in developing therapeutic strategies from an immunological standpoint.