Association between venous thromboembolism and atrial fibrillation: a Mendelian randomization study.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-10-29 DOI:10.1186/s12920-024-02034-y
Caijing Dang, Wenkai Liao, Lin Xu, Wenshu Zhao, Yuxia Lu
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Abstract

Background: Although previous observational studies have shown an association between venous thromboembolism (VTE) and atrial fibrillation (AF), the underlying causal relationship between them remains uncertain.

Methods and results: This two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal relationship between VTE and AF. The VTE dataset were obtained from FinnGen, including 9,176 cases and 209,616 controls. Meanwhile a genome-wide association study (GWAS) of 60,620 individuals with AF and 970,216 control subjects identified genetic variations associated with AF. The principal MR analytic approach used in this study is the inverse-variance weighting (IVW) method. Furthermore, we performed complementary MR analyses, including the MR-Egger, Weighted median (WM), and Weighted Mode. MR pleiotropy residual sum was applied to identify pleiotropy. The MR analysis showed suggestive causal associations between VTE and the risk of AF (p = 0.0245, OR [95%CI]: 1.027 [1.003, 1.051]). The reverse MR analysis found that genetic susceptibility to AF was not significantly associated with VTE, as determined by the IVW method (p = 0.7773). The robustness of these findings was corroborated through MR sensitivity analyses.

Conclusions: There is a unidirectional causal relationship between VTE and AF, meaning that VTE is a causal risk factor for AF, whereas no effect of AF on VTE was identified.

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静脉血栓栓塞与心房颤动之间的关系:孟德尔随机研究。
背景:尽管以往的观察性研究显示静脉血栓栓塞(VTE)与心房颤动(AF)之间存在关联,但它们之间的潜在因果关系仍不确定:该双样本双向孟德尔随机化(MR)分析旨在研究 VTE 与房颤之间的因果关系。VTE 数据集来自 FinnGen,包括 9,176 例病例和 209,616 例对照。与此同时,一项针对 60,620 名心房颤动患者和 970,216 名对照受试者的全基因组关联研究(GWAS)确定了与心房颤动相关的基因变异。本研究采用的主要磁共振分析方法是逆方差加权法(IVW)。此外,我们还进行了补充性 MR 分析,包括 MR-Egger、加权中位数 (WM) 和加权模式。MR 多效性残差总和用于识别多效性。MR分析显示,VTE与房颤风险之间存在提示性因果关系(p = 0.0245,OR [95%CI]:1.027 [1.003,1.051])。反向 MR 分析发现,根据 IVW 方法(p = 0.7773),心房颤动遗传易感性与 VTE 并无显著关联。这些结果的稳健性在磁共振敏感性分析中得到了证实:VTE与房颤之间存在单向因果关系,即VTE是房颤的一个因果风险因素,而房颤对VTE没有影响。
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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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