骨关节炎(OA)是最常见的肌肉骨骼疾病之一,也是老年人群疼痛和残疾的主要原因。金属蛋白(MPs)与OA关系的研究有限,因果关系尚不清楚。我们的目标是利用孟德尔随机化(MR)来探索MPs和OA之间可能的因果关系。关于MP的数据来源于涉及3301个样品的全基因组关联研究(GWAS)分析。OA的GWAS数据来自一项涉及462,933名欧洲个体的分析。在这项研究中,多种双样本孟德尔随机化方法(双样本MR)来评估MPs对OA的因果效应,包括逆方差加权法(IVW),MR-Egger方法,加权中位数法(WM),简单模式,重量模式,和Wald比率。使用IVW方法的主要MR分析揭示了金属硫蛋白-1F(MT-1F)之间的显着负相关,锌指蛋白134(ZNF134),钙/钙调蛋白依赖性蛋白激酶1D型(CAMK1D),和EF手含钙结合域蛋白14(EFCAB14)与骨关节炎(OA)的发生(p值<0.05)。然而,在这些MPs和OA之间没有观察到相反方向的因果关系.值得注意的是,即使在考虑混杂因素的组合模型中,这4种MPs与OA之间的负相关性仍然显著.敏感性分析表明没有水平多效性或异质性的证据,留一法分析证实了结果的稳健性。在这项研究中,我们已经在四个不同的议员和OA之间建立了明显的联系。这一发现增强了我们对诊断和治疗这种疾病的潜在途径的理解。要点•采用MR方法评估MPs与OA之间的关系。•总共四种类型的MPs已显示出对OA发生的抑制作用。
Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a primary cause of pain and disability among the elderly population. Research on the relationship between
metalloproteins (MPs) and OA is limited, and causality remains unclear. Our objective is to utilize Mendelian randomization (MR) to explore the possible causal relationship between MPs and OA. The data on MPs were derived from a Genome-Wide Association Study (GWAS) analysis involving 3301 samples. The GWAS data for OA were obtained from an analysis involving 462,933 European individuals. In this study, a variety of two-sample Mendelian randomization methods (two-sample MR) to evaluate the causal effect of MPs on OA, including inverse variance weighted method (IVW), MR-Egger method, weighted median method (WM), simple mode, weight mode, and Wald ratio. The primary MR analysis using the IVW method reveals a significant negative correlation between Metallothionein-1F (MT-1F), zinc finger protein 134 (ZNF134), calcium/calmodulin-dependent protein kinase type 1D (CAMK1D), and EF-hand calcium-binding domain-containing protein 14 (EFCAB14) with the occurrence of osteoarthritis (OA) (p value < 0.05). However, no causal relationship was observed in the opposite direction between these MPs and OA. Notably, even in combined models accounting for confounding factors, the negative association between these four MPs and OA remained significant. Sensitivity analysis demonstrated no evidence of horizontal pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the results. In this study, we have established a conspicuous association between four distinct MPs and OA. This discovery augments our understanding of potential avenues for the diagnosis and treatment of this condition. Key Points • The MR method was employed to assess the relationship between MPs and OA. • A total of four types of MPs have demonstrated inhibitory effects on the occurrence of OA.