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HYPOTHESIS AND THEORY article

Front. Cardiovasc. Med.
Sec. Cardiac Rhythmology
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1416412

Causal effect of vascular endothelial growth factor on the risk of atrial fibrillation: A two-sample Mendelian randomization study

Provisionally accepted
Han S. Liang Han S. Liang 1Xue Ling Xue Ling 2*Chen C. Hong Chen C. Hong 3Xie J. Min Xie J. Min 3Kong F. Chang Kong F. Chang 3Zhang Fang Zhang Fang 3
  • 1 Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 2 Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 3 Affiliated Hospital of Hebei University, Baoding, Hebei Province, China

The final, formatted version of the article will be published soon.

    Background: Observational studies have found that vascular endothelial growth factor (VEGF) levels are associated with the risk of cardiovascular disease. However, it remains unclear whether VEGF levels have a causal effect on the risk of atrial fibrillation.A two-sample Mendelian randomization (MR) study was conducted to explore the causal relationship between VEGF levels and the risk of atrial fibrillation.receptor-2 (VEGFR-2), VEGFR-3] and atrial fibrillation (atrial fibrillation, atrial fibrillation and flutter) were used as instrumental variables. Data on genetic variants were obtained from published genome-wide association studies (GWAS) or the IEU Open GWAS project. Inverse-variance weighted (IVW) analysis was used as the primary basis for the results, and sensitivity analyses were used to reduce bias. Causal relationships were expressed as odds ratio (OR) with 95% confidence interval (CI), and a P-value of <0.1 corrected for False Discovery Rate (FDR) (PFDR<0.1) was considered to have a significant causal relationship.: Genetically predicted high levels of VEGF-A [OR=1.025 (95%CI: 1.004-1.047), PFDR=0.060] and VEGF-D [OR=1.080 (95%CI: 1.039-1.123), PFDR=0.001)] were associated with an increased risk of atrial fibrillation, while no causal relationship was observed between VEGF-C (PFDR=0.419), VEGFR-2 (PFDR=0.784), and VEGFR-3 (PFDR=0.899) and atrial fibrillation risk. Moreover, only genetically predicted high levels of VEGF-D [OR=1.071 (95%CI: 1.014-1.132), PFDR=0.087] increased the risk of atrial fibrillation and flutter. Sensitivity analysis demonstrated that the relationship between VEGF-D levels and the risk of atrial fibrillation was robust.This study supports a causal association between high VEGF-D levels and increased risk of atrial fibrillation.

    Keywords: Atrial Fibrillation, causal association, Mendelian randomization, Vascular Endothelial Growth Factor, VEGF-D

    Received: 05 Jun 2024; Accepted: 27 Sep 2024.

    Copyright: © 2024 Liang, Ling, Hong, Min, Chang and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xue Ling, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei Province, China

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