Identifying the genetic association between rheumatoid arthritis and the risk of infectious diseases

Previous evidence suggests an association between rheumatoid arthritis (RA) and infectious diseases, but the causal relationship remains unclear. This study sought to explore causal associations between RA and five common infections: pneumonia, sepsis, urinary tract infections (UTI), skin and subcutaneous tissue infections (SSTI), and bacterial intestinal infections (BII).

To identify the causal links, we adopted a Mendelian randomization (MR) design utilizing the inverse variance weighted (IVW), weighted median (WM), and MR-Egger approaches. Univariable MR (UVMR) and multivariable MR (MVMR) analyses were performed using pooled genome-wide association studies (GWAS) data. Additionally, various sensitivity analyses were conducted to ensure the reliability of the results.

In the UVMR analysis, RA was potentially associated with elevated risks of pneumonia (OR = 1.034, 95% CI: 1.016-1.052, P < 0.001) and sepsis (OR = 1.079, 95% CI: 1.048-1.110, P = 3.507E-07). This association remained significant after adjusting for smoking, alcohol consumption, or type 2 diabetes mellitus (T2DM) in the MVMR analysis. However, no causal links were found between RA and UTI, SSTI, and BII. Sensitivity analyses showed no detectable heterogeneity or pleiotropy, strengthening the causal inference of results.

Our study provides strong evidence of the association between RA and increased risks of pneumonia and sepsis. Further research is required to validate these findings and elucidate the underlying mechanisms. Key Points • It remains unclear whether the increased susceptibility to infections in RA stems from a genetic predisposition or results from immunosuppressive treatments. • The MR method is employed to assess the relationship between RA and common infectious diseases. • Our MR study supports a potential causal relationship between RA and elevated risks of pneumonia and sepsis.