Two-sample Mendelian randomization analysis of the causal relationship between vascular endothelial growth factor A and inflammatory bowel disease
10.3760/cma.j.cn101480-20240116-00011
- VernacularTitle: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
- Author:
Longxiang ZHANG
1
;
Jian LI
1
;
Qiqi ZHANG
1
;
Zhiqiang ZHANG
1
;
Hongliang GAO
1
Author Information
1. 新疆医科大学第一附属医院消化病二科，乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
Vascular endothelial growth factor A;
Inflammatory bowel disease;
Ulcerative colitis;
Crohn's disease;
Mendelian randomization analysis
- From:
Chinese Journal of Inflammatory Bowel Diseases
2024;08(6):416-423
- CountryChina
- Language:Chinese
-
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.
