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

IF 2.8 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Frontiers in Cardiovascular Medicine Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI:10.3389/fcvm.2024.1416412

Siliang Han, Ling Xue, Chunhong Chen, Junmin Xie, Fanchang Kong, Fang Zhang

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Abstract

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.

Methods: A two-sample Mendelian randomization (MR) study was conducted to explore the causal relationship between VEGF levels and the risk of atrial fibrillation. Genetic variants associated with VEGF [VEGF-A, VEGF-C, VEGF-D, VEGF 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) (P_FDR < 0.1) was considered to have a significant causal relationship.

Results: Genetically predicted high levels of VEGF-A [OR = 1.025 (95%CI: 1.004-1.047), P_FDR = 0.060] and VEGF-D [OR = 1.080 (95%CI: 1.039-1.123), P_FDR = 0.001]] were associated with an increased risk of atrial fibrillation, while no causal relationship was observed between VEGF-C (P_FDR = 0.419), VEGFR-2 (P_FDR = 0.784), and VEGFR-3 (P_FDR = 0.899) and atrial fibrillation risk. Moreover, only genetically predicted high levels of VEGF-D [OR = 1.071 (95%CI: 1.014-1.132), P_FDR = 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.

Conclusion: This study supports a causal association between high VEGF-D levels and increased risk of atrial fibrillation.

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血管内皮生长因子对心房颤动风险的因果效应：双样本孟德尔随机研究。

背景：观察性研究发现，血管内皮生长因子（VEGF）水平与心血管疾病风险有关。然而，血管内皮生长因子水平对心房颤动风险是否有因果关系仍不清楚：方法：为探讨血管内皮生长因子水平与心房颤动风险之间的因果关系，我们进行了一项双样本孟德尔随机化（MR）研究。与血管内皮生长因子（VEGF-A、VEGF-C、VEGF-D、血管内皮生长因子受体-2（VEGFR-2）、VEGFR-3）和心房颤动（心房颤动、心房颤动和扑动）相关的基因变异被用作工具变量。遗传变异数据来自已发表的全基因组关联研究（GWAS）或 IEU Open GWAS 项目。结果以反方差加权（IVW）分析为主要依据，并使用敏感性分析来减少偏差。因果关系用带有 95% 置信区间 (CI) 的几率比（OR）和 PFDR 结果的 P 值表示：基因预测的高水平 VEGF-A [OR = 1.025 (95%CI: 1.004-1.047), PFDR = 0.060] 和 VEGF-D [OR = 1.080 (95%CI: 1.039-1.123), PFDR = 0.001]]与心房颤动风险增加有关，而 VEGF-C（PFDR = 0.419）、VEGFR-2（PFDR = 0.784）和 VEGFR-3（PFDR = 0.899）与心房颤动风险之间没有因果关系。此外，只有基因预测的高水平 VEGF-D [OR = 1.071（95%CI：1.014-1.132），PFDR = 0.087]会增加心房颤动和扑动的风险。敏感性分析表明，VEGF-D 水平与心房颤动风险之间的关系是稳健的：本研究支持高 VEGF-D 水平与心房颤动风险增加之间存在因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine

CiteScore

3.80

自引率

11.10%

发文量

3529

审稿时长

14 weeks

期刊介绍： Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.