TITLE:
Application of Integrated Chromatin Accessibility and Transcriptome Analysis in Atrial Fibrillation Research
AUTHORS:
Ming Chen, Shaning Yang
KEYWORDS:
Atrial Fibrillation, RNA Sequencing, Multi-Omics Analysis
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.11,
October
30,
2026
ABSTRACT: Atrial fibrillation (AF) is a common persistent arrhythmia that affects approximately 33 million people worldwide. The incidence of AF increases sharply with age. Its pathogenesis is extremely complex and mainly involves the interaction between cardiac electrophysiology and structural remodeling, inflammation, fibrosis, and metabolic disorders. Genome-Wide Association Studies (GWAS) have uncovered plenty of risk loci linked to atrial fibrillation; among these loci, PITX2, TBX5, ZFHX3 and PRRX1 represent some of the most well-studied genes. These genes take part in atrial tissue development, myocardial electrical conduction and gene transcriptional regulation. However, most genetic variants do not sit within coding sequences, and researchers still cannot figure out their exact biological functions. As multi-omics research keeps moving forward, increasing experimental evidence suggests that factors influencing AF-related genes mainly fall into two categories: one is inherited genetic variants, and the other covers altered chromatin structure and abnormal gene expression. Epigenetic regulatory patterns include DNA methylation, histone modification, chromatin remodeling and non-coding RNAs; these mechanisms can adjust gene expression without changing the original DNA base sequences. Chromatin accessibility analysis allows researchers to spot activated promoter and enhancer regions, and transcriptome analysis can measure how high or low gene expression levels are. When researchers combine ATAC-seq with RNA-seq, they can build connections between chromatin regulatory regions and gene transcription, so as to screen candidate regulatory segments, transcription factor networks and interactive relationships of genes related to atrial fibrillation. This combined research approach has been adopted in cardiovascular epigenetics experiments, and it helps researchers further interpret how non-coding variants work, as well as sort out internal regulatory networks of atrial fibrillation. Results from multiple integrated analyses show that AF-related risk variants mostly lie within cardiac-specific open chromatin regions; after researchers delete one single regulatory segment on the Tbx5 locus, gene dosage will get altered, and animals will gain higher susceptibility to arrhythmia. Single-cell multi-omics technologies further expand research scope in this field, and they enable researchers to investigate unique regulatory programs inside different cell types, such as cardiomyocytes, fibroblasts, endothelial cells and immune cells. This review sums up practical applications of combined chromatin-accessibility and transcriptome analysis in AF research; it describes disease-related regulatory segments, candidate genes, genetic risk loci, cell-specific functional mechanisms and potential therapeutic targets. Meanwhile, it lists existing research obstacles, including obvious sample heterogeneity, insufficient causal verification and the lack of unified analytical workflows. This paper also discusses future research directions, and technologies like single-cell multi-omics, spatial omics and artificial intelligence may push forward the development of precision medicine for atrial fibrillation.