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Potential causal association of a prolonged PR interval and clinical recurrence of atrial fibrillation after catheter ablation: a Mendelian randomization analysis

Abstract

A prolonged PR interval predicts atrial fibrillation (AF) recurrence after catheter ablation. We investigated the causal association between the PR interval and AF clinical recurrence by a Mendelian randomization. We prospectively included 1722 patients with AF (73.2% male, 58.6 ± 10.8 years old, 71.3% paroxysmal AF) who underwent catheter ablation into a genome-wide association study (GWAS). We searched for the genetic associations between the PR interval and AF recurrence by analyzing 44 single nucleotide polymorphisms (SNPs) already known to be associated with the PR interval, and investigated the Mendelian randomization. Based on the quartile analysis, the highest quartile of the PR interval was associated with an increased risk of AF recurrence compared with the lowest quartile (Hazard ratio (HR) = 1.91, 95% CI = 1.51–2.42, P = 8.41 × 10−8) during 35.7 ± 28.5 months of follow-up. Among 44 SNPs known to be associated with the PR interval, two SNPs had significant associations with the PR interval (P < 0.001 for each SNP). CAV1 (HR = 1.15, 95% CI = 1.02–1.31, P = 0.024) was associated with clinical recurrence of AF. A Mendelian randomization analysis demonstrated a significant association with CAV1 (HR = 1.04, 95% CI = 1.01–1.07, P = 0.006). A prolonged PR interval was a risk factor for an AF recurrence, and the PR interval had a potentially causal association with an AF clinical recurrence after catheter ablation at the genetic level.

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Acknowledgements

We would like to thank Mr. John Martin for his linguistic assistance. This work was supported by grants [HI18C0070 to PH-N] and [HI19C0114 to PH-N] from the Ministry of Health and Welfare, grants [NRF-2020R1A2B01001695 to PH-N] and [NRF-2019R1I1A1A01041440 to HM] from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, and the Brain Korea 21 PLUS Project for Medical Science, Yonsei University.

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Correspondence to Hui-Nam Pak.

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Hong, M., Hwang, I., Yu, HT. et al. Potential causal association of a prolonged PR interval and clinical recurrence of atrial fibrillation after catheter ablation: a Mendelian randomization analysis. J Hum Genet 65, 813–821 (2020). https://doi.org/10.1038/s10038-020-0774-2

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