基于孟德尔随机化以及Meta分析方法评估CX3CL1表达水平与系统性红斑狼疮的因果关系

doi:10.20223/j.cnki.1000-8535.2025.11.004

摘要/Abstract

摘要： 目的采用两样本孟德尔随机化以及Meta分析研究趋化因子C-X3-C基序配体1（CX3CL1）表达水平与系统性红斑狼疮（SLE）发病风险的因果关系。方法获取CX3CL1表达水平与SLE的全基因组关联研究（GWAS）数据,将单核苷酸多态性（SNP）作为工具变量并选择敏感的SNPs进行分析。通过逆方差加权法（IVW）、加权中位数法（WM）、MR-Egger回归法进行两样本MR分析,以OR值评估CX3CL1表达水平与SLE之间的因果关系,并对结果进行异质性和多效性检验。最后利用R软件Meta包进行Meta分析。利用coloc包进行共定位分析。结果纳入9个SLE作为结局变量,其中4个变量ebi-a-GCST90018917（OR=2.14,95%CI：1.50~3.06）,ebi-a-GCST003156（OR=2.25,95%CI：1.00~5.06）,ebi-a-GCST90014238（OR=3.02,95%CI：1.54~5.94）,finn-b-SLE_NOS（OR=1.81,95%CI：1.01~3.22）表明CX3CL1表达水平与SLE之间存在因果关系。关于 OR 95% CI 的森林图显示 SLE 患者的CX3CL1表达水平显著高于健康人群（OR=1.87,95% CI：1.53~2.29,P<0.001）。共定位分析结果提示CX3CL1表达水平和SLE表型之间有共享的遗传变异位点（rs170364）。结论 CX3CL1表达水平与SLE存在正向因果关系,CX3CL1表达水平的升高使得SLE的发病风险升高。

关键词: CX3CL1表达水平, 系统性红斑狼疮, 孟德尔, Meta分析

Abstract: Objective To investigate the causal relationship between CX3CL1 levels and the risk of systemic lupus erythematosus（SLE）using two-sample Mendelian randomization and Meta-analysis methods．Methods Genome-Wide Association Study（GWAS）data for CX3CL1 levels and SLE were obtained．Single nucleotide polymorphisms（SNPs）were used as instrumental variables,and sensitive SNPs were selected for analysis．Two-sample Mendelian randomization was performed using the inverse variance weighted（IVW）method,weighted median（WM）method,and MR-Egger regression to evaluate the causal relationship between CX3CL1 levels and SLE,with OR values assessing this relationship．Heterogeneity and pleiotropy tests were conducted on the results．Meta-analysis was performed using the Meta package in R software,and colocalization analysis was conducted using the coloc package．Results Nine SLE outcomes were included as outcome variables,with four variables（ebi-a-GCST90018917[OR=2.14,95%CI：1.50-3.06],ebi-a-GCST003156[OR=2.25,95%CI：1.00-5.06],ebi-a-GCST90014238[OR=3.02,95%CI：1.54-5.94],finn-b-SLE_NOS[OR=1.81,95%CI：1.01-3.22]）indicating a causal relationship between CX3CL1 expression levels and SLE．The forest plot for OR 95% CI showed that CX3CL1 expression levels in SLE patients were significantly higher than in healthy individuals（OR=1.87[95%CI：1.53-2.29],P<0.001）．Colocalization analysis suggested that there was shared genetic variation sites（rs170364）between CX3CL1 expression levels and SLE phenotype．Conclusions There is a positive causal relationship between CX3CL1 expression levels and SLE,with increased CX3CL1 levels elevating the risk of developing SLE．

Key words: CX3CL1 expression levels, systemic lupus erythematosus, Mendelian randomization, Meta-analysis

董翠翠, 赵志虎. 基于孟德尔随机化以及Meta分析方法评估CX3CL1表达水平与系统性红斑狼疮的因果关系[J]. 广州医药, 2025, 56(11): 1491-1500.

DONG Cuicui, ZHAO Zhihu. Causal relationship between CX3CL1 expression levels and systemic lupus erythematosus based on Mendelian randomization and Meta-analysis[J]. Guangzhou Medical Journal, 2025, 56(11): 1491-1500.

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