University of Maryland School of Medicine, Baltimore.
University of Maryland School of Medicine and Veterans Administration Maryland Health Care System, Baltimore.
Arthritis Care Res (Hoboken). 2024 Mar;76(3):366-375. doi: 10.1002/acr.25252. Epub 2024 Feb 7.
Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA.
This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms "osteoarthritis" and ("Mendelian randomization" or "polygenic risk score"). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions.
Our search identified 45 studies reporting on 141 exposure-association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P < 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR-Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low-density lipoprotein cholesterol.
These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk.
孟德尔随机化（MR）越来越多地被用作建立可改变的暴露因素与骨关节炎（OA）之间因果关系的工具。本综述的目的是总结现有的评估可改变的危险因素对 OA 因果作用的 OA 的 MR 研究。
本综述遵循系统评价和荟萃分析（PRISMA）扩展的首选报告项目（PRISMA）扩展范围评价模式进行。我们使用“骨关节炎”和（“孟德尔随机化”或“多基因风险评分”）等搜索词，在多个数据库中搜索 2021 年 12 月之前发表的相关研究。我们报告了暴露与 OA 之间因果关联的 MR 估计值，然后根据其验证三个关键 MR 假设的努力评估抽象研究的方法学质量。
我们的搜索确定了 45 项研究，报告了 141 项暴露关联分析。所有研究都进行了正式的工具变量分析，以估计暴露对 OA 的因果影响。在这些分析中有 60 项报告了因果关联（P < 0.05），代表 36 篇独特的出版物，其中 45 项进行了 MR-Egger 敏感性分析。MR 研究支持 OA 与肥胖水平升高、咖啡摄入、骨密度和睡眠障碍以及血清钙和低密度脂蛋白胆固醇水平降低之间的因果关联。
这些结果强调了减轻体重和改善睡眠质量以降低 OA 风险的潜在益处，并呼吁更好地了解咖啡摄入和血清钙与 OA 风险的关系。
