■在欧洲血统的遗传水平上探索强直性脊柱炎(AS)和骨关节炎(OA)之间的双向因果关系。
■我们实施了一系列质量控制步骤,以选择与暴露有关的工具变量(IV)。我们使用逆方差加权方法作为主要方法进行了两个样本孟德尔随机化(MR)。我们使用Bonferroni校正调整了显著性水平,使用Cochrane的Q检验评估异质性。采用留一法进行敏感性分析。此外,采用了外部数据集和宽松的IV选择标准,和多变量MR分析用于验证目的。最后,贝叶斯共定位(COLOC)分析确定了常见基因,验证MR结果。
■这项研究的重点是膝关节OA和AS之间的相关性,臀部,和手关节。MR结果显示,AS患者膝关节OA的风险降低(OR=0.9882,95%CI:0.9804-0.9962),但髋关节OA的风险没有显着增加(OR=0.9901,95%CI:0.9786-1.0018)。相反,AS是手部OA的危险因素(OR=1.0026,95%CI:1.0015-1.0036)。在反向MR分析中,OA对AS的发生没有显著影响。重要的是,在我们的MR分析结果中观察到最小的异质性(p>0.05),通过敏感性分析和多变量MR分析证实了这些结果的稳健性.COLOC分析确定了AS和手部OA的四种共定位变体(rs74707996、rs75240935、rs181468789和rs748670681)。
■在欧洲人口中,患有AS的个体患膝关节OA的风险相对较低,而AS是手部OA的危险因素。然而,AS与髋关节OA之间没有显著的因果关系。此外,它为AS和OA的遗传研究提供了新的见解。
To explore the bidirectional causal relationship between Ankylosing Spondylitis (AS) and Osteoarthritis (OA) at the genetic level within the European ancestry.
We implemented a series of quality control steps to select instrumental variables (IVs) related to the exposure. We conducted two-sample Mendelian randomization (MR) using the inverse-variance weighted method as the primary approach. We adjusted significance levels using Bonferroni correction, assessed heterogeneity using Cochrane\'s Q test. Sensitivity analysis was conducted through leave-one-out method. Additionally, external datasets and relaxed IV selection criteria were employed, and multivariate MR analyses were performed for validation purposes. Finally, Bayesian colocalization (COLOC) analysis identified common genes, validating the MR results.
The investigation focused on the correlation between OA and AS in knee, hip, and hand joints. MR results revealed that individuals with AS exhibit a decreased risk of knee OA (OR = 0.9882, 95% CI: 0.9804-0.9962) but no significant increase in the risk of hip OA (OR = 0.9901, 95% CI: 0.9786-1.0018). Conversely, AS emerged as a risk factor for hand OA (OR = 1.0026, 95% CI: 1.0015-1.0036). In reverse-direction MR analysis, OA did not significantly influence the occurrence of AS. Importantly, minimal heterogeneity was observed in our MR analysis results (p > 0.05), and the robustness of these findings was confirmed through sensitivity analysis and multivariate MR analysis. COLOC analysis identified four colocalized variants for AS and hand OA (rs74707996, rs75240935, rs181468789, and rs748670681).
In European population, individuals with AS have a relatively lower risk of knee OA, whereas AS serves as a risk factor for hand OA. However, no significant causal relationship was found between AS and hip OA. Additionally, it offers novel insights into genetic research on AS and OA.