Abstract
Background: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. Methods: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran’s Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. Results: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95 % confidence interval (CI), 1.009 – 1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (β = -0.021, 95 % CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. Conclusions: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.
RAS ID
54055
Document Type
Journal Article
Date of Publication
12-1-2022
Volume
20
Issue
1
Funding Information
National Nature Science Foundation of China (NFSC 81673247) / China-Australian collaborative grant (NSFC 81561128020-NHMRC APP1112767) / National Key R&D Program of China (2018YFC2000704)
School
Centre for Precision Health
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Springer
Recommended Citation
Zhang, Q., Zhang, X., Zhang, J., Wang, B., Tian, Q., Meng, X., Zhang, J., Jiang, M., Zhang, Y., Zheng, D., Wu, L., Wang, W., Wang, B., & Wang, Y. (2022). Vascular endothelial growth factor and the risk of venous thromboembolism: A genetic correlation and two-sample Mendelian randomization study. DOI: https://doi.org/10.1186/s12959-022-00427-6
Comments
Zhang, Q., Zhang, X., Zhang, J., Wang, B., Tian, Q., Meng, X., ... & Wang, Y. (2022). Vascular endothelial growth factor and the risk of venous thromboembolism: A genetic correlation and two-sample Mendelian randomization study. Thrombosis Journal, 20, Article 67. https://doi.org/10.1186/s12959-022-00427-6