Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
The Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
J Orthop Surg Res. 2024 Sep 28;19(1):608. doi: 10.1186/s13018-024-05107-x.
Knee osteoarthritis (KOA), hallux valgus (HV) and hallux rigidus (HR) are common musculoskeletal problems of the lower extremities. However, their underlying causal relationships are unclear. This study attempts to clarify the cause-and-effect relationship between KOA and the two common hallux deformities (HV and HR).
The summary-level statistics for KOA, HV, and HR were collected from genome-wide association studies (GWAS). The causal analysis of KOA on HV or HR was carried out using two-sample Mendelian randomization (MR). In order to assess the robustness of the MR results, sensitivity analyses were performed. In addition, multivariable MR (MVMR) was implemented to assess the influence of KOA in causation as well as calibrate the effect of anthropometric characteristics. Supplementary backward MR analysis was conducted to determine the causal effect of hallux diseases on KOA.
The univariable analysis indicated that KOA has a causative influence on HR (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.18-1.41, P = 2.25E-8) and HV (OR = 1.43, 95% CI = 1.21-1.68, P = 2.76E-5). In the backward MR analyses, hallux deformities did not appear to be the cause of KOA. In the MVMR analysis, after jointly adjusting for the effects of waist-to-hip ratio (WHR), waist circumference (WC), hip circumference (HC) and BMI, the causal impact of KOA on HV and HR remained robust.
In this study, the genetic causality between KOA and increased risk of hallux deformities (HV and HR) is established, which can provide evidence-based recommendations for reducing the incidence of hallux deformities in KOA patients. Further high-level studies are warranted to validate the associations and explore its broader implications.
膝骨关节炎（KOA）、拇外翻（HV）和僵直性拇囊炎（HR）是下肢常见的肌肉骨骼问题。然而，它们之间的因果关系尚不清楚。本研究试图阐明 KOA 与两种常见的拇趾畸形（HV 和 HR）之间的因果关系。
从全基因组关联研究（GWAS）中收集了 KOA、HV 和 HR 的汇总水平统计数据。使用两样本 Mendelian 随机化（MR）分析 KOA 对 HV 或 HR 的因果关系。为了评估 MR 结果的稳健性，进行了敏感性分析。此外，还进行了多变量 Mendelian 随机化（MVMR）分析，以评估 KOA 在发病机制中的影响，并校准人体测量特征的作用。进行了补充反向 Mendelian 分析，以确定拇趾疾病对 KOA 的因果影响。
单变量分析表明，KOA 对 HR（比值比 [OR] = 1.29，95%置信区间 [CI] = 1.18-1.41，P = 2.25E-8）和 HV（OR = 1.43，95% CI = 1.21-1.68，P = 2.76E-5）具有因果影响。在反向 Mendelian 分析中，拇趾畸形似乎不是 KOA 的原因。在 MVMR 分析中，在共同调整腰臀比（WHR）、腰围（WC）、臀围（HC）和 BMI 的影响后，KOA 对 HV 和 HR 的因果影响仍然稳健。
本研究确立了 KOA 与拇趾畸形（HV 和 HR）风险增加之间的遗传因果关系，为降低 KOA 患者拇趾畸形的发病率提供了循证建议。需要进一步的高级研究来验证这些关联，并探讨其更广泛的意义。
