Rheumatoid arthritis and risk of lung diseases in East Asians and Europeans: Evidence from a Mendelian randomization study

Background: Rheumatoid arthritis might increase the risk of lung diseases, such as interstitial lung disease and lung cancer. However, the causal relationships remained unclear. Herein, we utilized Mendelian randomization to study the causal relationships. Material and methods: Genetic Data from European ancestry and East Asian ancestry were used. The main Mendelian randomization approaches included inverse variance weighted, weighted median, and Mendelian randomization-Egger. We also conducted a series of analyses to validate the robustness of the Mendelian randomization estimates by integrating complementary Mendelian randomization models, Cochran’s Q test, Mendelian randomization-Egger intercept analysis, leave-one-out analysis, RadialMR, Steiger filtering test, multivariable Mendelian randomization and colocalization analysis. Results: In East Asian, inverse variance weighted indicated a significant association between rheumatoid arthritis and lung cancer after Bonferroni correction (odds ratio = 1.11, 95% confidence interval: 1.05–1.18); in both East Asian and European ancestries, rheumatoid arthritis was found to increase risk for interstitial lung disease (odds ratio East Asian = 1.29, 95% confidence interval: 1.17–1.42, which remained significant after Bonferroni correction; odds ratio European = 1.08, 95% confidence interval: 1.02–1.16). The observed significant associations between rheumatoid arthritis and interstitial lung disease remained in both ancestries after accounting for smoking behavior in multivariable Mendelian randomization analyses. The detected impact of rheumatoid arthritis on the risk of lung cancer in East Asian ancestry vanished after adjusted with smoking initiation. Conclusion: Using Mendelian randomization analysis, our results unveiled that rheumatoid arthritis augmented the risks of IL, independent of smoking initiation in both European and East Asian ancestry. These revelations might have implications for clinicians to be more vigilant and enhance routine interstitial lung disease screening in rheumatoid arthritis patients.