基于孟德尔随机化分析探讨凝血因子与肝细胞癌的因果关系
Exploring the causal relationship between coagulation factors and hepatocellular carcinoma based on Mendelian randomization analysis
摘要
Abstract
Objective:To investigate the causal relationship between coagulation factors(vWF,ADAMTS13,APTT,FⅧ,FⅪ,FⅦ,FⅩ,D-Dimer,Fibrinogen,Prothrombin,PAI-1,Protein C,Plasmin)and the risk of hepatocellular carcinoma(HCC)using a two-sample Mendelian randomization(MR)approach.Methods:Genetic data for 13 coagulation factors were ob-tained from published genome-wide association studies.The data for HCC came from the Finnish Biobank.The inverse variance weighted(IVW)method was used as the primary analysis approach,supplemented by the weighted median method,MR-Egger regression,simple mode,and weighted mode for analysis.Heterogeneity testing,horizontal pleiotropy analysis,and sensitivity analysis were also conducted.Multivariable MR analysis was performed to adjust for the effects of the 13 coagulation factors us-ing the IVW method.Results:The univariate MR results showed a positive causal relationship between ADAMTS13,FⅪ,Prothrombin,PAI-1,and HCC,while Plasmin,vWF,APTT,and FⅦ showed a negative causal relationship with HCC.No causal relationship was found between other coagulation factors and the risk of HCC(P>0.05).Sensitivity analysis indicated that the causal relationships were robust,and the MR-Egger intercept analysis did not detect potential horizontal pleiotropy.Af-ter multivariable MR adjustment,the negative correlation between APTT and HCC remained significant(OR=0.08,95%CI:0.01-0.87,P=0.037),while ADAMTS13 showed an independent positive causal relationship with HCC(OR=1.84,95%CI:1.09-3.10,P=0.021).IVW method result showed no causal relationship between HCC and the 13 coagulation factors(P>0.05).Conclusion:This study elucidates the coagulation factors causally associated with HCC using genetic tools,providing po-tential targets for disease intervention and contributing to early screening and prevention.关键词
孟德尔随机化/凝血因子/肝细胞癌Key words
Mendelian randomization/Coagulation factor/Hepatocellular carcinoma分类
医药卫生引用本文复制引用
LI Jiongfen,HU Mengling,LIN Yong,ZENG Yangling,ZHANG Kan,ZHANG Riyun,WANG Tingshuai,WANG Minggang,MAO Dewen..基于孟德尔随机化分析探讨凝血因子与肝细胞癌的因果关系[J].海南医科大学学报,2025,31(23):1812-1822,11.基金项目
This study was supported by the National Natural Science Foundation of China(82360912,81960841,82274434) （82360912,81960841,82274434）
Guangxi Traditional Chinese Medicine Interdisciplinary Innovation Team Project(GZKJ2306) （GZKJ2306）
Natural Science Foundation Project of Guangxi Province(2023GXNSFBA026190) （2023GXNSFBA026190）
Doctoral Research Initiation Fund Project of Guangxi University of Chinese Medicine(2021BS028) （2021BS028）
Research Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2021QN004) 国家自然科学基金项目(82360912、81960841、82274434) （2021QN004）
广西中医药多学科交叉创新团队项目(GZKJ2306) （GZKJ2306）
广西自然科学基金项目(2023GXNSFBA026190) （2023GXNSFBA026190）
广西中医药大学博士科研启动基金项目(2021BS028) （2021BS028）
广西中医药大学第一附属医院科研项目(2021QN004) （2021QN004）
