Association Between Rheumatoid Arthritis and Multiple Chronic Respiratory Diseases and Lung Function:A Mendelian Randomization Study Based on GWAS Database

YANG Yang; SHEN Si; LUO Xiang; WANG Zhixia; ZHANG Zhiqiang

doi:10.3969/j.issn.1004-437X.2026.09.001

Abstract：Objective A two-sample Mendelian randomization(MR)analysis was conducted to examine the causal association between rheumatoid arthritis(RA)and asthma,chronic obstructive pulmonary disease(COPD),bronchiectasis,and lung function.Methods This MR analysis was performed using genetic variants as instruments which were related with RA(462 933 cases),asthma(463 010 cases),COPD(361 194 cases),bronchiectasis(462 933 cases)and lung function[forced expiratory volume in one second/forced vital capacity(FEV1/FVC)](51 396 cases)from the available genome-wide association studies(GWAS)to explore the causal effects on RA and multiple chronic respiratory diseases and lung function.Instrument variables were included in accord with P＜5 × 10-8,linkage disequilibrium r2=0.001 and the width of the linked imbalance region was 10 Mb.The MR estimates from each genetic instrument were combined using the random-effect,inverse-variance weighted(IVW)analysis as the primary method.Sensitivity,pleiotropy,MR-pleiotropy residual sum and outlier(MR-PRESSO)and heterogeneity analyses were then performed to estimate the robustness of those findings.Results Based on the above analysis method,it was concluded that there was a causal relationship between RA and asthma(ORIVW=2.084,95％CI:1.672-2.598,P=6.31 × 10-11)and COPD(ORIVW=1.072,95％CI:1.030-1.115,P=6.24 × 10-4).However,no causal relationship was found between RA and bronchiectasis(ORIVW=1.110,95％CI:0.911-1.351,P=0.300)or FEV1/FVC(ORIVW=0.696,95％CI:0.133-3.642,P=0.668).Conclusion The MR results support that RA can increase the risk of asthma and COPD,and there is a causal relationship.However,no causal association was found between the risk of bronchiectasis and FEV1/FVC.These results can provide high-quality causal evidence for clinical practice as well as for the pathogenesis and prevention of chronic respiratory diseases induced by rheumatoid arthritis.