Key result
Genetic predisposition to lone AF linked to ~162% higher stroke risk and increased heart failure.
Why the study?
Lone atrial fibrillation occurs without discernible risk factors, but its long-term prognostic implications remain unclear.
Does genetic predisposition to lone atrial fibrillation increase the risk of cardiovascular diseases?
Does genetic predisposition to lone atrial fibrillation increase the risk of cardiovascular diseases?
Effect estimate: OR 2.62 for stroke; OR 2.55 for heart failure; OR 0.90 for coronary artery disease; OR 1.32 for cardiac death (95% CI 95% CI 2.14–3.22 for stroke; 2.14–3.04 for heart failure; 0.73–1.10 for coronary artery disease; 0.99–1.77 for cardiac death)
p-value: p=2.8 × 10^−20 for stroke; 1.4 × 10^−25 for heart failure; 0.307 for coronary artery disease; 0.059 for cardiac death
Genetic predisposition to lone atrial fibrillation is associated with a more than twofold increased risk of stroke and heart failure, highlighting its significant long-term prognostic implications despite the absence of traditional risk factors.
May guide genetic risk stratification for stroke/HF surveillance in lone AF; leaves open causal confirmation and intervention trials.
Background: Lone atrial fibrillation (AF) is characterized by the absence of discernible risk factors, yet its long-term prognostic implications remain unclear. We evaluated genetic predisposition to lone AF and conducted a Mendelian randomization (MR) study to assess its causal effect on cardiovascular outcomes. Methods: A genome-wide association study (GWAS) for lone AF, along with common AF was conducted using UK Biobank data. Lone AF was defined as AF occurring without clinical risk factors. Summary-level data for cardiovascular phenotypes were obtained from publicly available GWAS datasets and the causal effects were estimated using MR. Results: We identified 36 single-nucleotide polymorphisms associated with lone AF, including two novel loci. In MR analyses, lone AF was significantly associated with an increased risk of stroke (odds ratio [OR] 2.62, 95% confidence interval [CI] 2.14–3.22) and heart failure (HF) (OR 2.55, 95% CI 2.14–3.04). The associations with coronary artery disease (CAD) (OR 0.90, 95% CI 0.73–1.10) and cardiac death (OR 1.32, 95% CI 0.99–1.77) were not significant. MR analyses of common AF also demonstrated significant associations with stroke (OR 1.86, 95% CI 1.69–2.04) and HF (OR 1.71, 95% CI 1.59–1.84), though the effect sizes were smaller compared to those of lone AF. Conclusions: Genetic predisposition to lone AF is associated with more than a twofold increase in the risk of stroke and HF. However, no clear association was observed between lone AF and CAD or cardiac death.
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Park et al. (2026) studied lone atrial fibrillation (n=459,119). genetic predisposition to lone atrial fibrillation vs. non-genetic predisposition (controls) was evaluated on risk of stroke, heart failure, coronary artery disease and cardiac death (OR 2.62 for stroke; OR 2.55 for heart failure; OR 0.90 for coronary artery disease; OR 1.32 for cardiac death, 95% CI 95% CI 2.14–3.22 for stroke; 2.14–3.04 for heart failure; 0.73–1.10 for coronary artery disease; 0.99–1.77 for cardiac death, p=2.8 × 10^−20 for stroke; 1.4 × 10^−25 for heart failure; 0.307 for coronary artery disease; 0.059 for cardiac death). Genetic predisposition to lone atrial fibrillation was associated with a 2.62-fold increased risk of stroke and a 2.55-fold increased risk of heart failure, with no significant association to coronary artery disease or cardiac death.
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