Key result
High AF polygenic risk linked to ~2.3-fold higher incident AF in mitral valve disease.
Why the study?
Atrial fibrillation in valvular heart disease is generally attributed to pressure or volume overload with atrial remodeling, leaving the independent contribution of genetic predisposition across valve subtypes unclear.
Does an atrial fibrillation polygenic risk score predict incident atrial fibrillation across different subtypes of valvular heart disease?
Cohort (n=452,841)
Does an atrial fibrillation polygenic risk score predict incident atrial fibrillation across different subtypes of valvular heart disease?
Hazard Ratio: 2.3
p-value: p=0.002
Genetic predisposition to atrial fibrillation significantly influences AF risk in mitral valve disease, particularly mitral valve prolapse, but has minimal impact in aortic valve disease.
AF PRS was associated with incident AF in VHD; supports genetic contribution but leaves open clinical utility.
BACKGROUND: Atrial fibrillation (AF) in valvular heart disease (VHD) is generally attributed to pressure or volume overload with atrial remodeling, but the independent contribution of genetic predisposition remains unclear. OBJECTIVES: The authors evaluated the predictive value of a previously developed AF polygenic risk score (PRS) across VHD subtypes in the UK Biobank. METHODS: In this prospective cohort study (UK Biobank, 2000-2022), incident AF and VHD status were defined using ICD codes. VHD subtypes included mitral valve (MV) disease (MV prolapse [MVP], mitral regurgitation, mitral stenosis) and aortic valve (AV) disease (aortic stenosis, aortic regurgitation). PRS was categorized into quintiles and grouped as low, intermediate, and high. RESULTS: Among 452,841 participants with available PRS, 385 had MVP, 1,058 mitral regurgitation, 81 mitral stenosis, 421 aortic regurgitation, and 509 aortic stenosis. In Cox models, PRS was independently associated with incident AF in MV disease (HR: 1.7, P = 0.03 for intermediate PRS; HR: 2.3, P = 0.002 for high PRS), with the strongest effect in MVP (HR: 3.1, P = 0.03 for high PRS). In AV disease, PRS was not significantly associated with AF risk (P = 0.93 and P = 0.07 for intermediate and high PRS, respectively). Interaction analyses confirmed attenuation or absence of the PRS effect in AV disease (P = 0.04 and P = 0.004 for intermediate and high PRS, respectively), whereas no significant interaction was observed in MV disease (P = 0.80 and P = 0.11, respectively). CONCLUSIONS: In VHD, AF PRS predicts AF risk, but the genetic impact differs by subtype. AV disease shows minimal genetic contribution, suggesting predominantly hemodynamic risk, while MV disease-particularly MVP-shows substantial genetic influence.
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Cristin et al. (2026) conducted a cohort in Valvular heart disease (n=452,841). High atrial fibrillation polygenic risk score (PRS) vs. Low polygenic risk score was evaluated on Incident atrial fibrillation in mitral valve disease (HR 2.3, p=0.002). A high polygenic risk score was significantly associated with an increased risk of incident atrial fibrillation in mitral valve disease (HR 2.3, P=0.002), but not in aortic valve disease.
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