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

Comparative and Functional Genomics Pub Date : 2026-02-23 DOI:10.1155/ijog/8056288

Dong Ye, Zhiping Zhang, Jun Zhang

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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循环代谢因子介导肥胖相关指标对半月板损伤的影响：一项孟德尔随机研究。

背景：半月板损伤和肥胖是全球主要的公共卫生问题。孟德尔随机化方法可以克服传统观察性研究设计在混杂和反向因果关系方面的局限性。本研究的目的是利用磁共振分析来评估肥胖相关指标与半月板损伤之间的因果关系，并探讨潜在的潜在机制。方法：从已发表的全基因组关联研究（genome-wide association studies， GWAS）中下载7项肥胖相关指标和11项循环代谢指标作为工具变量，并使用FinnGen数据库的半月板损伤数据作为结局指标。采用双样本单变量MR、多变量MR和中间MR分析因果关系和中介因素。应用Bonferroni调整后,IVW模型表明,五个与肥胖相关的指标,即腰围(p < 0.001,或= 1.6333),体重指数(p < 0.001,或= 1.5175),体脂百分比(p < 0.001,或= 1.5449),左(p < 0.001,或= 1.9432)/右(p < 0.001,或= 1.9099)腿部脂肪比例,增加半月板损伤的风险,和全身骨矿物质密度(p = 0.0014,或者= 1.1098)也增加了半月板损伤的风险。核磁共振鉴定的因果关系方向一致，无水平多效性。多变量和介导的磁共振分析显示，体脂率的有害影响可能是由血清尿酸水平介导的。结论：我们的研究表明，由体脂率驱动的血清尿酸水平升高可能会增加半月板损伤的风险。我们希望这些发现将为半月板损伤的预防和治疗提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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