The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation.

Ban Liu,Yongjun Qian,Xin Shi,Keke Ding,Mengwei Lv,Shijie Zhu,Changfa Guo,Yangyang Zhang

doi:10.3389/fbioe.2020.00187

Abstract

Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.

Highlights

Atrial fibrillation (AF), one of the most prevalent heart rhythm disorders, is a potential cause of heart failure and ischemic stroke with high morbidity and mortality (Ogawa et al, 2017; Asmarats et al, 2019)
DNA methylation, a pre-transcriptional modification characterized by the addition of methyl groups to specific nucleotides, regulates the stability of gene expression states and maintains genome integrity by collaborating with proteins that modify nucleosomes (Ma et al, 2014; Tao et al, 2016; Shen et al, 2017)
Previous studies considered that changes in DNA methylation states contribute to the regulation of biological processes underlying AF, such as fibrosis, atrial dilatation, atrial fibroblast proliferation and differentiation from fibroblasts into myofibroblasts (Zhao et al, 2017)

Summary

Introduction

Atrial fibrillation (AF), one of the most prevalent heart rhythm disorders, is a potential cause of heart failure and ischemic stroke with high morbidity and mortality (Ogawa et al, 2017; Asmarats et al, 2019). The cause of AF is multifactorial which include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction (Schnabel et al, 2009; Lip et al, 2013; Voukalis et al, 2016). In contrast to the extensive knowledge of etiology, the underlying mechanism of AF remains elusive. Further study of the potential mechanisms of AF could provide novel strategies for the treatment and management to increase quality of life and reduce economic burden of social (Chugh et al, 2001)

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Conclusion