JACC Advances · Oct 20, 2026

Atrial Fibrillation in Valvular Heart Disease: Assessing the Impact of Genetics in the UK Biobank

By Cristin L, Tang JJ, Tastet L et al.

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.

doi.org/10.1016/j.jacadv.2026.103355Open accessPubMed 42901089Biomarkers