Introduction:
This study aims to elucidate the potential impact of whole body water mass on osteoarthritis at the genetic prediction level through a two-sample Mendelian randomization (MR) analysis.

Material and methods:
Using summary data from genome-wide association studies, we obtained information on whole body water mass and various forms of osteoarthritis, including knee and hip Osteoarthritis, knee osteoarthritis, and hip osteoarthritis from a large-scale genome-wide association study. MR analysis used inverse variance weighting, weighted median, MR-Egger, simple mode, and weighted estimation. Sensitivity analyses, including the MR-Egger method, MR-PRESSO, Cochran's Q-test, and leave-one-out assessment, were performed to assess the reliability of the results.

Results:
In the inverse variance weighting model, increased genetic susceptibility to whole body water mass was significantly associated with knee and hip Osteoarthritis, knee osteoarthritis, and hip osteoarthritis (OR=1.45, 95% CI:1.27–1.65, p=3.24×10-08; OR=1.53, 95% CI:1.30–1.79, p=2.18×10-07; OR=1.25, 95% CI:1.04-1.50, p=0.02). These results indicate a positive causal relationship between whole body water mass and osteoarthritis. The MR-Egger intercept and Cochran's Q-test indicated the absence of heterogeneity and horizontal pleiotropy in the analyses of whole body water mass and knee and hip Osteoarthritis, knee osteoarthritis, and hip osteoarthritis.

Conclusions:
The MR analysis suggests a positive correlation between whole body water mass and the risk of osteoarthritis.