解放军医学院学报2025，Vol.46Issue(9)：869-874,896,7.DOI:10.12435/j.issn.2095-5227.25051901
双样本孟德尔随机化分析炎症因子与骨关节炎的因果关系
Two-sample Mendelian randomization analysis for causal relationships between inflammatory factors and osteoarthritis
摘要
Abstract
Background Studies have found that inflammatory factors are closely associated with the progression of osteoarthritis,but the relationship between inflammatory factors and osteoarthritis(OA)remains unclear.Objective To analyze the causal relationship between 91 inflammatory factors and OA using Mendelian randomization(MR).Methods Genome-wide association study(GWAS)data of 91 inflammatory factors and OA were obtained.The inverse variance weighted method(IVW)was used as the main method,and four other methods,including MR-Egger regression,were used as supplementary methods to evaluate the causal effect.Sensitivity analysis was conducted using Cochran Q,MR-PRESSO,MR-Egger intercept test,and leave-one-out analysis.Results MR analysis identified five inflammatory factors significantly associated with OA(all P＜0.05):chemokine ligand 4(CCL4),chemokine ligand 23(CCL23),tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),chemokine ligand 11(CCL11),and interleukin-20 receptor α(IL-20Rα).The IVW method yielded the following odds ratios(ORs)and 95%confidence intervals(CIs):CCL4(OR=1.002 6,95%CI:1.000 8-1.004 5),CCL23(OR=0.997 7,95%CI:0.995 5-0.999 8),TRAIL(OR=0.996 9,95%CI:0.994 4-0.999 3),CCL11(OR=0.996 9,95%CI:0.993 9-0.999 9),and IL-20Rα(OR=0.995 8,95%CI:0.991 8-0.999 8).Sensitivity analyses showed no evidence of heterogeneity(Cochran's Q test),outliers(MR-PRESSO test),or horizontal pleiotropy(MR-Egger intercept test),with leave-one-out analysis further confirming the robustness of the results.Conclusion MR analysis supports potential causal relationships between these inflammatory factors and OA,identifying CCL4 as a risk factor and CCL23,TRAIL,CCL11,and IL-20Rα as protective factors.关键词
炎症/炎症因子/骨关节炎/孟德尔随机化/全基因组关联研究Key words
inflammation/inflammatory factors/osteoarthritis/Mendelian randomization/genome-wide association study分类
医药卫生引用本文复制引用
孔德策,张岩,邵进,张莲卿..双样本孟德尔随机化分析炎症因子与骨关节炎的因果关系[J].解放军医学院学报,2025,46(9):869-874,896,7.基金项目
上海市浦东新区卫生健康委员会优秀青年医学人才培养计划(PWRq2021-45) （PWRq2021-45）
上海市浦东新区卫生系统重点学科(PWZxk2022-09) （PWZxk2022-09）
上海市浦东新区公利医院青年英才(GLRq2020-06) （GLRq2020-06）
