孟德尔随机化探究类风湿性关节炎与冠状动脉疾病因果关系以及步行速度的介导作用

Objective It is believed that patients with rheumatoid arthritis (RA) have an increased risk of developing coronary arteiy disease (CAD). Due to joint pain/stiffness or other joint problems, physical fitness (e.g. walking speed) is oflen reduced in RA patients. However, the causal link between RA, usual walking pace, and CAD remains unclear. Here we aimed to examine the causal association between RA and CAD by using Mendelian randomization (MR). Whether usual walking pace mediates the causal pathway from RA to CAD was also assessed. Methods Summary statistics from genome-wide association studies (GWASs) were un«d for 2-sample MR analyses. There were 103688 samples in HA data, 547261 samples in CAD data and 452264 samples in usual walking pace data. MR analysis was performed using inverse variance weighting method and weighted median method. Hie final estimation was evaluated by MR-Egger and leave-one-out analyses. Results MR analyses showed that RA was positively associated with the risk of CAD (OR = 1.03，95% C/: 1.01-1.04, P = 3.90x10"5) and negatively associated with usual walking pacc (fi = -0.02,95% CI: -0.04 0.01, P = 3,15 x 10"4). Significant negalive causal effect of usual walking pace on CAD was also observed {OR = 0.841, 95% CI: 0.81-0.88, P = 3.43x10_IJ). Mediation analysis showed that usual walking pace might account for about 15.8% of the association between RA and incident CAD. Conclusion In conclusion, our results indicate that RA may be causally associated with increased risk of CAD and usual walking pace might mediate a significant proportion of the relationship between RA and CAD.