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Updated: Jun 30, 2026

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The Genetics of Atrial Fibrillation: From Molecular Mechanisms to Precision Medicine

Dilip D Hinge1, Abhijeet Shelke2, Ramesh Kawade2

  • 1Molecular Biology and Genetics, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, IND.

Cureus
|June 29, 2026
PubMed

Insights

Genetic factors significantly contribute to atrial fibrillation (AF) susceptibility. This review details AF-associated genes and their functional roles, paving the way for precision medicine in cardiac electrophysiology.

Area of Science:

  • Cardiology
  • Genetics
  • Molecular Biology

Background:

  • Atrial fibrillation (AF) is the most common cardiac arrhythmia.
  • While aging and comorbidities are factors, AF has a significant heritable component.
  • Genetic predisposition plays a substantial role in AF susceptibility.

Purpose of the Study:

  • To systematically review the molecular landscape of AF.
  • To focus on genetic mutations and their functional consequences in AF development.
  • To provide a framework for precision medicine in cardiac electrophysiology.

Main Methods:

  • Systematic review of AF-associated genes.
  • Categorization of genes into functional modules: ion channelopathies, structural myopathies, transcriptional regulators, and calcium handling proteins.
  • Discussion of population prevalence, variant penetrance, and molecular/biophysical consequences of mutations.

Main Results:

  • Identified four functional modules of AF-associated genes: ion channelopathies (e.g., SCN5A), structural myopathies (e.g., TTN), transcriptional regulators (e.g., PITX2), and calcium handling proteins (e.g., RYR2).
  • Detailed the specific consequences of causative mutations for each gene.
  • Elucidated how protein alterations converge on shared electrophysiological and structural substrates.

Conclusions:

  • Genetic mutations in specific functional modules significantly contribute to AF.
  • Understanding these genetic underpinnings allows for a transition from generalized treatments to precision medicine.
  • This molecular framework supports personalized therapeutic strategies in cardiac electrophysiology.

Keywords:
atrial fibrillationcardiac arrhythmiageneticsion channelsprecision medicinetranscription factors

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