Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Beijing, China.
Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Immunol. 2024 Oct 3;15:1453685. doi: 10.3389/fimmu.2024.1453685. eCollection 2024.
To better understand the preventive or therapeutic clinical interventions that may be supported by the association between rheumatoid arthritis (RA) and postural deformities including hallux valgus, flat foot, and scoliosis, this study was conducted using Mendelian randomization (MR) analysis. It aimed to investigate whether RA is causally associated with postural deformities in European populations.
Summary-level data on RA and postural deformities were obtained from the IEU OpenGWAS project and Finngen database, respectively. LDSC regression analysis was conducted to assess the genetic correlation between these diseases. The inverse variance weighting (IVW) method was employed as the primary approach for two-sample MR analyses to evaluate causality. Supplementary methods included MR-Egger, maximum likelihood, weighted median, and cML-MA. To test for potential horizontal pleiotropy, we performed the MR-Egger intercept test, cML-MA, and secondary analyses after excluding confounders. Additionally, mediation analyses were conducted using two-step MR.
The IVW method revealed RA to be causally associated with hallux valgus (OR 1.132, 95% CI 1.087-1.178, P < 0.001) and flat foot (OR 1.197, 95% CI 1.110-1.291, < 0.001). Among postural deformities, hallux valgus was causally associated with flat foot (OR 1.823, 95% CI 1.569-2.119, < 0.001) and scoliosis (OR 1.150, 95% CI 1.027-1.287, < 0.05). No significant horizontal pleiotropy was detected. Moreover, mediation analyses indicated that hallux valgus mediates the effect of RA on flat foot (mediation effect 0.024, 95% CI 0.005-0.044, < 0.05), with a mediation proportion of 41.31%.
These findings indicate a potential causal association between genetically predicted RA and both hallux valgus and flat foot. Furthermore, hallux valgus serves as a mediator in the pathway from RA to flat foot. This underscores the importance of early screening and preventive treatment of foot deformities in RA patients. Further research is necessary to determine the applicability of these findings in non-European populations.
为了更好地理解类风湿关节炎 (RA) 与包括拇外翻、平足和脊柱侧凸在内的姿势畸形之间可能存在的预防或治疗临床干预，本研究采用孟德尔随机化 (MR) 分析进行。目的是探讨 RA 是否与欧洲人群的姿势畸形存在因果关系。
RA 和姿势畸形的汇总水平数据分别从 IEU OpenGWAS 项目和 Finngen 数据库中获得。LDSC 回归分析用于评估这些疾病之间的遗传相关性。作为两样本 MR 分析的主要方法，采用逆方差加权（IVW）方法评估因果关系。补充方法包括 MR-Egger、最大似然、加权中位数和 cML-MA。为了检验潜在的水平多效性，我们进行了 MR-Egger 截距检验、cML-MA 和排除混杂因素后的二次分析。此外，还通过两步 MR 进行中介分析。
IVW 方法表明 RA 与拇外翻（OR 1.132，95%CI 1.087-1.178，P<0.001）和扁平足（OR 1.197，95%CI 1.110-1.291，<0.001）存在因果关系。在姿势畸形中，拇外翻与扁平足（OR 1.823，95%CI 1.569-2.119，<0.001）和脊柱侧凸（OR 1.150，95%CI 1.027-1.287，<0.05）存在因果关系。未检测到明显的水平多效性。此外，中介分析表明，拇外翻介导了 RA 对扁平足的影响（中介效应 0.024，95%CI 0.005-0.044，<0.05），中介比例为 41.31%。
这些发现表明，遗传预测的 RA 与拇外翻和扁平足之间存在潜在的因果关系。此外，拇外翻是 RA 导致扁平足的中介因素。这凸显了早期筛查和预防 RA 患者足部畸形的重要性。需要进一步的研究来确定这些发现在非欧洲人群中的适用性。
