血管内皮生长因子A与炎症性肠病因果关系的两样本孟德尔随机化研究
Two-sample Mendelian randomization analysis of the causal relationship between vascular endothelial growth factor A and inflammatory bowel disease
张龙祥 1李健 1张琪琪 1张志强 1高鸿亮1
作者信息
- 1. 新疆医科大学第一附属医院消化病二科,乌鲁木齐 830054
- 折叠
摘要
目的 采用两样本单向孟德尔随机化(MR)分析探讨血管内皮生长因子A(VEGF-A)与炎症性肠病(IBD)的因果关系.方法 选择基于91种炎症蛋白相关的全基因组关联研究(GWAS)数据集,以及英国生物银行(UK Biobank)和IEU OpenGWAS Project样本库中IBD相关GWAS数据,以VEGF-A为暴露因素,筛选与IBD相关的单核苷酸多态性(SNP)作为遗传变异工具变量.采用两样本单向MR分析中逆方差加权法(IVW)为主要方法分析VEGF-A与IBD的潜在因果关系.利用Cochran's Q检验检测潜在异质性,利用MR-PRESSO方法及MR-Egger截距检验评估水平多效性,采用留一法进行敏感性分析.结果 GWAS数据来源于UK Biobank及IEU OpenGWAS Project数据库,共包含4 355例UC患者及2 128例CD患者.IVW结果显示,经过Bonferroni校正后VEGF-A在 UC 的发病中可能发挥保护作用(OR=0.9993,95％CI:0.9985～0.99997,P=0.0421;OR=0.9991,95％CI:0.9984～0.9998,P=0.0095),与CD未发现存在因果关系的证据(P=0.5024;P=0.3150).在应用Meta分析合并MR分析后,结果提示VEGF-A是UC的保护性因素(OR=0.9992,95％CI:0.9987～0.9997,P=0.0011),而与 CD无因果关系(OR=1.0000,95％CI:0.9997～1.0004,P=0.8352).Cochran's Q检验结果提示不存在异质性;MR-Egger截距项结果提示不存在水平多效性;MR-PRESSO异常值检验未发现离群值;留一法敏感性分析未见异常SNP;提示MR分析的因果推断具有一定的可靠性.结论 通过MR分析得出VEGF-A与UC风险降低具有因果关系,而与CD之间并无因果关系.
Abstract
Objective To explore the causal relationship between vascular endothelial growth factor A(VEGF-A)and inflammatory bowel disease(IBD)using two-sample unidirectional Mendelian randomization(MR)analysis.Methods Datasets based on genome-wide association studies(GWAS)of 91 inflammation-related proteins and GWAS datasets related to IBD were collected from the UK Biobank and the IEU OpenGWAS Project.With VEGF-A as the exposure factor,single nucleotide polymorphisms(SNP)associated with IBD were screened as genetic instrumental variables.The inverse variance weighted(IVW)approach served as the primary method in the two-sample unidirectional MR analysis was used to examine the potential causal link between VEGF-A and IBD.Cochran's Q test was utilized to detect potential heterogeneity,while the MR-PRESSO method and MR-Egger intercept test were employed to assess horizontal pleiotropy.A leave-one-out analysis was conducted to evaluate the sensitivity of the results.Results GWAS data were sourced from the UK Biobank and the IEU OpenGWAS Project databases,including a total of 4 355 UC patients and 2 128 CD patients.The IVW results suggested that VEGF-A may play a protective role in the onset of UC after Bonferroni correction(OR=0.9993,95％CI:0.9985～0.99997,P=0.0421;OR=0.9991,95％CI:0.9984～0.9998,P=0.0095),while no evidence of causal relationship with CD was found(P=0.5024,P=0.3150).Subsequent meta-analysis of the MR results indicated that VEGF-A was a protective factor for UC(OR=0.9992,95％CI:0.9987～0.9997,P=0.0011),while no causal association with CD was found(OR=1.0000,95％CI:0.9997～1.0004,P=0.8352).The results of Cochran's Q test indicated no heterogeneity,the MR-Egger intercept suggested no horizontal pleiotropy,the MR-PRESSO outlier test detected no outliers,and the leave-one-out sensitivity analysis revealed no abnormal SNP,indicating that the causal inference from the Mendelian randomization analysis had a certain level of reliability.Conclusion Mendelian randomization analysis indicates causal relationship between VEGF-A and reduced risk of UC,but no causal relationship is found between VEGF-A and CD.
关键词
血管内皮生长因子A/炎症性肠病/溃疡性结肠炎/克罗恩病/孟德尔随机化分析Key words
Vascular endothelial growth factor A/Inflammatory bowel disease/Ulcerative colitis/Crohn's disease/Mendelian randomization analysis引用本文复制引用
出版年
2024
NETL
NSTL
万方数据