Bidirectional causal relationship between rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization study

BACKGROUND: Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are systemic, autoimmune inflammatory diseases. Although overlapping clinical and genetic features have been reported, the presence of a direct causal relationship between them remains uncertain. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was performed using genetic variants as instrumental variables to evaluate potential causal associations between RA and SLE. Sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy and the robustness of the findings. RESULTS: Genetically predicted RA did not have a significant causal effect on susceptibility to SLE. Conversely, genetically predicted SLE did not demonstrate a significant causal effect on RA risk. Sensitivity analyses supported the stability and reliability of these findings, with no evidence of substantial heterogeneity or directional pleiotropy. CONCLUSION: We concluded that RA and SLE may share genetic susceptibility and environmental triggers without a unidirectional causal relationship.