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Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study

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Abstract

Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran’s Q test, “Leave-one-out,” and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998–1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, − 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE.

Graphical abstract

Causal effect of atrial fibrillation on pulmonary embolism: a Mendelian randomization study. AF atrial fibrillation, PE pulmonary embolism, GWAS genome-wide association studies, SNPs single nucleotide polymorphisms, OR odds ratio, CI confidence interval.

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Funding

This work was financially supported by National Natural Science Foundation of China (81201788).

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Authors and Affiliations

  1. Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, 610041, Sichuan, China

    Guihong Liu, Xin Zhang, Binbin Hu & Huashan Shi

  2. Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China

    Tao Chen

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  1. Guihong Liu
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  2. Tao Chen
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  3. Xin Zhang
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  4. Binbin Hu
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Correspondence to Huashan Shi.

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11239_2023_2903_MOESM1_ESM.xlsx

Characteristics of SNPs used as instrumental variables for atrial fibrillation. SNP, single nucleotide polymorphism; SE, standard error; R2 = 2*(1 − eaf)*eaf*(beta)2; F = (R2/1 − R2)(N-2). Supplementary material 1 (XLSX 25.5 kb)

Mendelian randomization analysis of atrial fibrillation on pulmonary embolism. Supplementary material 2 (XLSX 19.1 kb)

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Liu, G., Chen, T., Zhang, X. et al. Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study. J Thromb Thrombolysis 57, 212–219 (2024). https://doi.org/10.1007/s11239-023-02903-w

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