Circulating Metabolic Factors Mediating the Effect of Obesity-Related Indicators on Meniscal Injuries: A Mendelian...

Meniscal injuries and obesity are major global public health problems. The Mendelian randomization approach can overcome the limitations of traditional observational study designs with respect to confounding and reverse causation. The aims of the current study are to assess the causal relationship between obesity-related indicators and meniscal injuries using MR analyses and to explore the potential underlying mechanism.

In total, seven obesity-related indicators and 11 circulating metabolic indicators were downloaded as instrumental variables from published genome-wide association studies (GWAS), and the meniscal injury data from the FinnGen database was used as the outcome indicators. The causal relationships and mediating factors were analyzed using two-sample univariate MR, multivariate MR, and intermediate MR.

After applying the Bonferroni correction, the IVW model indicated that five obesity-related indicators, namely, waist circumference (p < 0.001, OR = 1.6333), BMI (p < 0.001, OR = 1.5175), body fat percentage (p < 0.001, OR = 1.5449), and left (p < 0.001, OR = 1.9432)/right (p < 0.001, OR = 1.9099) leg fat percentage, increased the risk of meniscal injuries, and total body bone mineral density (p = 0.0014, OR = 1.1098) also increased the risk of meniscal injury. The direction of MR-identified causal relationships was consistent without horizontal pleiotropy. Multivariate and mediated MR analyses revealed that the hazardous effects of body fat percentage might be mediated by serum uric acid levels.

Our study suggests that increases in serum uric acid levels, driven by body fat percentage, may increase the risk of meniscal injuries. We hope that these findings will provide new insights for the prevention and treatment of meniscal injury.