[1]时 元,翁 震,许 杰,等.基于UKBB、FinnGen和相关大型队列联盟数据应用双向两样本孟德尔随机化分析评估41种炎症细胞因子对AS及血栓发生的因果影响[J].现代检验医学杂志,2026,41(03):133-141.[doi:10.3969/j.issn.1671-7414.2026.03.024]
　SHI Yuan,WENG Zhen,XU Jie,et al.Bidirectional Two-Sample Mendelian Randomization Analysis Using UKBB, FinnGen, and Related Large Cohort Consortium Data to Assess the Causal Effects of 41 Inflammatory Cytokines on Atherosclerosis and Thrombosis[J].Journal of Modern Laboratory Medicine,2026,41(03):133-141.[doi:10.3969/j.issn.1671-7414.2026.03.024]
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基于UKBB、FinnGen和相关大型队列联盟数据应用双向两样本孟德尔随机化分析评估41种炎症细胞因子对AS及血栓发生的因果影响()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第41卷
期数:
2026年03期
页码:
133-141
栏目:
论著
出版日期:
2026-05-13

文章信息/Info

Title:
Bidirectional Two-Sample Mendelian Randomization Analysis Using UKBB, FinnGen, and Related Large Cohort Consortium Data to Assess the Causal Effects of 41 Inflammatory Cytokines on Atherosclerosis and Thrombosis
文章编号:
1671-7414（2026）03-133-09
作者:
时 元1a,1b，翁 震1a,1b，许 杰2a，陈宗艺1a,1b，何 杨1a,2b，沈霞红2c
1.苏州大学 a. 唐仲英医学研究院；b. 血液与血管疾病诊疗药物教育部工程中心，江苏苏州215123；2. 苏州大学附属第一医院 a. 输血科；b. 江苏省血液学研究所，卫生部血栓与止血重点实验室；c.肾内科，江苏苏州 215006
Author(s):
SHI Yuan1a,1b, WENG Zhen1a,1b, XU Jie2a, CHEN Zongyi1a1b,HE Yang1a,2b, SHEN Xiahong2c
1a. Cyrus Tang Hematology Center; 1b. MOE Engineering Center of Hematological Disease, Soochow University, Suzhou 215123, China; 2a. Department of blood transfusion; 2b. MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology; 2c. Department of Nephrology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
关键词:
动脉粥样硬化; 血栓; 炎症细胞因子; 双向两样本孟德尔随机化
分类号:
R543；R446
DOI:
10.3969/j.issn.1671-7414.2026.03.024
文献标志码:
A
摘要:
目的通过双向两样本孟德尔随机化(MR)分析探讨炎症细胞因子对动脉粥样硬化（AS）及血栓发生的因果影响。方法基于英国生物银行(UKBB)数据库、芬兰生物样本库（FinnGen）及其他大型队列联盟的全基因组关联研究（GWAS）数据应用双向两样本MR分析评估41种炎症细胞因子与8种AS及8种血栓发生的因果关系，并行异质性和多效性分析。同时对不同来源数据行meta组合分析及多变量MR分析。结果MR和Meta分析的结果均显示白细胞介素（IL）-10与深静脉血栓（DVT）、干细胞生长因子-β（SCGF-β）与肺栓塞（PE）、IL-10与冠状动脉粥样硬化、碱性成纤维细胞生长因子（FGF-Basic）与下肢血栓存在因果关联（均P<0.001）。基于UKBB数据的多变量MR结果显示，肿瘤坏死因子-α（TNF-α）与PE和DVT、静脉炎与血栓性静脉炎和静脉血栓栓塞症存在因果关联（均P<0.05）；而基于FinnGen数据的结果则显示嗜酸性粒细胞趋化因子（EOTAXIN）和静脉血栓栓塞症、白细胞介素-2受体α链（IL-2RA）与慢性肾脏病存在因果关联（均P<0.05）。结论不同类型的炎症细胞因子在AS及动静脉相关血栓发生中的作用有差异，提示不同种类细胞因子可能通过不同机制在AS及动静脉血栓发生中发挥作用。
Abstract:
Objective To explore the causal effects of inflammatory cytokines on atherosclerotic (AS) and thrombotic outcomes via a bidirectional two-sample Mendelian randomization (MR) analysis. Methods A bidirectional two-sample MR analysis was performed for exploration of the causal relationships between 41 inflammatory cytokines and 8 AS and 8 thrombotic outcomes using genome-wide association study (GWAS) data from the UK Biobank (UKBB), FinnGen and large cohort consortium stud-ies. The heterogeneity and pleiotropy analyses were performed concurrently. Meta-combination analysis and multivariate MR analysis were conducted across data sources. Results Both MR and Meta-analysis results showed causal associations between IL-10 and deep vein thrombosis (DVT) of lower extremities, and between stem cell growth factor-β (SCGF-β) and pulmo-nary embolism (PE), between IL-10 and coronary atherosclerosis, and between fibroblast growth factor basic (FGF-Basic) and thrombosis of lower extremity (all P<0.001). Multivariable MR analysis based on UKBB data revealed causal associations between tumor necrosis factor-α (TNF-α) and PE , DVT, phlebitis and thrombophlebitis, venous thromboembolism(VTE) (all P<0.05). FinnGen data revealed causal associations between eosinophil chemotactic factor (EOTAXIN) and VTE,IL-2RA and chronic kidney disease (CKD) (all P<0.05). Conclusions Different types of inflammatory cytokines play different roles in AS and arteriovenous thrombosis, suggesting that various cytokines may act through different mechanisms in AS and ar-teriovenous thrombosis.

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备注/Memo

备注/Memo:
基金项目：国家自然基金面上项目（82070123），苏州市科技计划（SKJY2021050），国家级大学生创新创业训练计划项目（202210285071Z）。
作者简介：时元（2000-），女，硕士，研究方向：血栓止血，E-mail：shiyuan02212022@163.com。
通讯作者： 沈霞红（1987-），女，博士，副主任医师，研究方向：血管及慢性肾病，E-mail：njsxh87@163.com。
何杨（1963-），男，本科，主任技师，研究方向：血栓止血，E-mail
更新日期/Last Update: 2026-05-15