Smoking can increase the risk of osteoarthritis in European women.

The effect of smoking on osteoarthritis remains controversial and its effect on osteoarthritis of different genders remains unclear. This study aimed to identify the causality in different sexes and to identify the mediating effect of obesity. A two-sample mendelian randomization analysis was performed using summary data from a previous genome-wide association study and UK biobank. Analyses were performed using three methods and inverse variance weighted analysis was used as the primary method. In addition to the overall effect, the effects of smoking on osteoarthritis were evaluated separately in both sexes. The reliability of the results was evaluated using Cochran's Q test, MR-Egger intercept test, MR PRESSO, and leave-one-out analysis. The R software was used for the analysis. There were 73 SNPs used as instrumental variables. The primary results supported that smoking led to an increased risk of osteoarthritis in both sexes (overall: OR 1.020, 95%CI 1.012-1.029; women: OR 1.024, 95%CI 1.013-1.035; men: OR 1.016, 95%CI 1.006-1.026). However, the secondary outcome did not support the effect of smoking on men (OR 0.997, 95%CI 0.949-1.047). Cochran's Q test and MR-PRESSO test indicated that there might be some outliers in the analysis (all p < 0.05), while potential outliers were not found. The MR egger regression, funnel plots, and sensitivity analyses supported the robustness of the results. Mediation analysis confirmed the mediating role of obesity. Smoking increases the risk for osteoarthritis in European, especially in women, and smoking education should be recommended.