Objective: Osteoarthritis (OA) is one of the major disabling human diseases. The related studies indicate a potential correlation between walking and OA. However, there is still a lack of evidence in genetics to support the correlation between walking and OA. Therefore, this study aimed to explore the relationship between walking and OA at the genetic level.

Methods: The publicly available Genome Wide Association Study (GWAS) data were used, with inverse variance weighting (IVW, the random-effects model) as the main analysis method, whereas MR-Egger, Weighted median, Simple mode, and Weighted mode as the secondary analysis methods. In addition, Cochran's Q test, pleiotropy test, and MR-Egger intercept test were conducted to examine the heterogeneity and pleiotropy of the outcome.

Results: In the MR analysis, IVW results showed a negative correlation between types of physical activity in last 4 weeks: Walking for pleasure (not as a means of transport) and OA (KOA or HOA) (odds ratio (OR) = 0.3224, 95% confidence interval (CI): 0.1261 to 0.8243), and the difference was of statistical significance (P = 0.0181). Moreover, IVW results also revealed a negative correlation between types of physical activity in last 4 weeks: Walking for pleasure (not as a means of transport) and KOA (OR = 0.1396, 95% CI: 0.0484 to 0.4026), and the difference was statistically significant (P = 0.0003). However, IVW results did not demonstrate any statistical significance types of physical activity in last 4 weeks: Walking for pleasure (not as a means of transport) and HOA (OR = 1.2075, 95% CI: 0.1978 to 7.3727, P = 0.8381).

Conclusion: From genetic studies, types of physical activity in last 4 weeks: Walking for pleasure (not as a means of transport) is negatively correlated with knee osteoarthritis (KOA), but there is no clear evidence supporting its correlation with hip osteoarthritis (HOA).