Work

Causality of atrial fibrillation and left atrial traits: Genetic and epigenetic perspectives

Year: 2025

Type: article

Abstract: Background Atrial fibrillation (AF) is associated with left atrial (LA) abnormalities, yet the causality between them are not well defined. Objective This study aims to investigate the genetic correlations and bidirectional causality between AF and LA traits. Methods We utilized Genome-Wide Association Study (GWAS) data from FinnGen and other cohorts. Linkage disequilibrium score regression (LDSC) was applied for estimates of genetic correlations, and Mendelian Randomization (MR) analysis was conducted for causality analysis. Results LDSC revealed significant genetic correlations between LA traits and AF. Forward MR analyses established causal associations of AF on LA active emptying fraction (LAaEF) (β: -0.092, P=2.29E-14), LA minimum volume (LAmin) (β: 0.083, P=1.11E-11), and LA maximum volume (β: 0.063, P=5.43E-08), while no causal relationship was observed with LA passive emptying fraction (LApEF). Reverse MR indicated a causal effect of LAaEF on AF (OR: 0.736, P=0.003). Epigenetic MR identified three CpG sites for AF (cg27529934, cg13639451, and cg07191189) which showed causal relationships with LA traits. Moreover, LA traits were causally associated with heart failure (LAaEF: OR: 0.879, P=0.013; LAmin: OR: 1.119, P=0.037) and cardioembolic stroke (LAaEF: OR: 0.689, P=0.010; LApEF: OR: 0.556, P=0.002; LAmin: OR: 1.733, P=0.045). Conclusions LAaEF is bidirectionally causally linked with AF, underscoring its importance in the management of AF. Epigenetic modifications, as evidenced by specific CpG sites, may contribute to atrial remodeling in AF, offering new avenues for research into the AF pathophysiology.

Source: Heart Rhythm O2

DOI: 10.1016/j.hroo.2025.10.018

Authors: Dihui Cai, Jie Xu, Yuheng Jiao, Yinyin Shen, Yingying Liao, Wei Han

Institutions: Tongji University, Shanghai East Hospital

Language: English

Topic: Atrial Fibrillation Management and Outcomes

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,150