A Genetic Causal Association Study between Genu Varum/ Valgus Deformity and Knee Osteoarthritis

Corresponding author: zhengyongzhi, zyz15838066078@126.com

DOI: 10.12201/bmr.202512.00057

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  Abstract: Objective To evaluate the potential causal relationship between genu varus/valgus deformity and knee osteoarthritis (KOA) using a two-sample bidirectional Mendelian randomization (MR) analysis. Methods This study utilized summary statistics derived from large-scale GWAS meta-analyses. The primary analysis employed the Inverse Variance Weighted (IVW) method, supplemented by MR-Egger regression, weighted median, weighted mode, and simple mode methods to investigate the causal association between genu varus/valgus deformity and KOA. Sensitivity analyses were conducted to assess the robustness of the MR findings. A reverse MR analysis was performed using the same methods. Results MR analysis revealed, based on genetic data, evidence for a causal effect of KOA on the risk of genu varus/valgus deformity OR = 1.686, 95% CI (1.379, 2.060), P = 3.38×10??. Sensitivity analyses confirmed the robustness of this association. However, no evidence was found for a causal effect of genu varus/valgus deformity on the risk of KOA. Conclusion This study provides strong evidence that KOA has a causal effect on increasing the risk of genu varus/valgus deformity, identifying it as a risk factor for its development and progression. Effective prevention and treatment of KOA may reduce the incidence or progression of knee deformity. Further in-depth research is warranted to elucidate the underlying mechanisms.

  Key words: Genu Varus/Valgus Deformity; Knee Osteoarthritis; Mendelian Randomization; Causal Inference

  Submit time: 19 December 2025

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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  1	2025-12-03	10.12201/bmr.202512.00057V1	Download

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