医学新知2025，Vol.35Issue(12)：1438-1443,中插6-中插8,9.DOI:10.12173/j.issn.1004-5511.202501004
组织蛋白酶与自身免疫性甲状腺疾病的因果关联:来自孟德尔随机化研究的探索
Causal relationship between cathepsins and autoimmune thyroid diseases:insights from a Mendelian randomization study
摘要
Abstract
Objective To explore the causal relationship between cathepsins and autoimmune thyroid diseases(AITDs)using Mendelian randomization(MR)study,and to provide genetic evidence for the association between cathepsins and the risk of AITDs.Methods The pooled datasets of nine cathepsins(B,E,F,G,H,L2,O,S and Z)and four AITDs were selected from a publicly available genome-wide association study(GWAS)website.The generalized summary data-based MR(GSMR),univariate bidirectional MR,and multivariate MR(MVMR)were used to analyze the causal relationship between them and the independent effects of specific risk factors.Plasma protein quantitative trait loci(pQTL)genetic instrumental variables were obtained from the Ferkingstad study to verify causality at the protein level.The inverse variance weighted method(IVW)was used as the primary analytical approach of univariate bidirectional MR Analysis,supplemented by MR-Egger,weighted median method,simple model,and weighted model methods.Horizontal pleiotropy and heterogeneity were evaluated,and sensitivity analysis was performed to ensure the robustness of the results.Results GSMR and forward MR analysis showed that cathepsin F(CTSF)significantly reduced the risk of Graves disease(GD).Reverse MR Analysis showed no reverse causality between the GD and CTSF.After adjusting for the effects of other cathepsins,MVMR analysis confirmed that the correlation between CTSF and GD was still significant.Furthermore,the causal effect between CTSF and GD was verified by cis-pQTL MR.Conclusion There is a causal relationship between CTSF and the reduced risk of GD,and CTSF is a potential protective factor against GD.关键词
组织蛋白酶/自身免疫性甲状腺疾病/孟德尔随机化/因果关联Key words
Cathepsins/Autoimmune thyroid diseases/Mendelian randomization/Causal relationship分类
医药卫生引用本文复制引用
YIN Meiqi,MOU Zongping,YU Pengcheng,SONG Xiudao..组织蛋白酶与自身免疫性甲状腺疾病的因果关联:来自孟德尔随机化研究的探索[J].医学新知,2025,35(12):1438-1443,中插6-中插8,9.基金项目
国家自然科学基金青年科学基金项目(82305088) （82305088）
苏州市姑苏卫生人才计划人才科研项目(GSWS2021048) （GSWS2021048）
苏州市科技发展计划项目(SKY2022204、SKY2023218) （SKY2022204、SKY2023218）
江苏省中医药科技发展计划项目(MS2024079) （MS2024079）
