The Causal Relationship Between Rheumatoid Arthritis and Pneumonia: A Mendelian Randomization Study

Abstract Background At present, it is not clear whether there is a causal relationship between rheumatoid arthritis (RA) and pneumonia. Method Single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study (GWAS) of RA, were used as instrumental variables. Inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode and weighted mode methods were used to investigate causal effects. We applied MR-PRESSO methods and MR–Egger methods to investigate sensitivity. The heterogeneity of individual genetic variants was evaluated by Cochran's Q test and a leave-one-out analysis. Results Forty-two SNPs were selected as instrumental variables. The results of the IVW method were very significant (OR, 1.056 for pneumonia per log-odds increment in RA risk, 95% CI 1.034–1.077; p = 1.87E-07), and other methods were also statistically significant. The results of the IVW method showed a causal effect of genetically determined RA on pneumonia (critical care) (OR, 1.053, 95% CI 1.001–1.106; p = 0.044) but no causal effect of genetically determined RA on pneumonia (death) or pneumonia (28-day death in critical care) Conclusions The study showed that RA was associated with an increased risk of pneumonia, but it did not cause death or a need for critical care.