BibTex format
@article{da:2026:10.1016/j.jacc.2025.12.014,
author = {da, Rocha GL and Feiner, J and Lazarte, J and Pang, K and Li, Y and Le, A and Man, A and Pathan, N and Whitlock, RP and Belley-Côté, EP and Conen, D and Wong, JA and McIntyre, WF and Healey, JS and Bezzina, CR and Watkins, H and Ware, JS and Tadros, R and Paré, G and Roberts, JD},
doi = {10.1016/j.jacc.2025.12.014},
journal = {J Am Coll Cardiol},
title = {Cardiomyopathy Gene Variants and Polygenic Risk Scores in Atrial Fibrillation: Evidence for an Atrial-First Phenotype.},
url = {http://dx.doi.org/10.1016/j.jacc.2025.12.014},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Atrial fibrillation (AF) is heritable and its complex underlying genetic substrate is gradually being unraveled. OBJECTIVES: We sought to explore the impact of disease-causing cardiomyopathy variants on the risk of AF after adjustment for incident ventricular cardiomyopathy and clinical heart failure in 2 cohort studies (UK Biobank [UKB] and All of Us [AoU]) and evaluate the utility of polygenic risk scores (PRS) to further discern the risk of atrial and ventricular phenotypes in carriers. METHODS: Cox regression was used to evaluate for associations between disease-causing variants within genes for 3 cardiomyopathies (dilated cardiomyopathy [DCM], hypertrophic cardiomyopathy [HCM], and arrhythmogenic right ventricular cardiomyopathy) and AF. Disease-specific PRSs for AF, DCM, and HCM stratified study participants into quintiles. A HR random-effects meta-analysis was performed using the DerSimonian-Laird method. The Kaplan-Meier method was used to ascertain cumulative incidence from birth to 75 years of age. RESULTS: Among 655,796 individuals from UKB and AoU, presence of a disease-causing variant was associated with an increased AF hazard (HR: 1.73; 95% CI: 1.59-1.89; P < 0.001), including after adjustment for incident ventricular cardiomyopathy or clinical heart failure (adjusted to HR: 1.55; 95% CI: 1.46-1.64, P < 0.001). The cumulative AF risk for study participants with a putative disease-causing rare variant and a PRSAF within the top-risk quintile ranged from 32.5% (UKB) to 32.4% (AoU) relative to 9.8% (UKB) and 11.0% (AoU) for individuals without a putative disease-causing variant and a PRSAF within the lowest-risk quintile. The absolute cumulative cardiomyopathy risk among study participants with both a putative disease-causing variant and a disease-specific PRS within the top-risk quintile ranged from 5.9% (UKB) to 15.2% (AoU) for DCM and from 11.7% (UKB) to 19.1% (AoU) for HCM. CONCLUSIONS: Genetic variants that cause cardiomyopathy also
AU - da,Rocha GL
AU - Feiner,J
AU - Lazarte,J
AU - Pang,K
AU - Li,Y
AU - Le,A
AU - Man,A
AU - Pathan,N
AU - Whitlock,RP
AU - Belley-Côté,EP
AU - Conen,D
AU - Wong,JA
AU - McIntyre,WF
AU - Healey,JS
AU - Bezzina,CR
AU - Watkins,H
AU - Ware,JS
AU - Tadros,R
AU - Paré,G
AU - Roberts,JD
DO - 10.1016/j.jacc.2025.12.014
PY - 2026///
TI - Cardiomyopathy Gene Variants and Polygenic Risk Scores in Atrial Fibrillation: Evidence for an Atrial-First Phenotype.
T2 - J Am Coll Cardiol
UR - http://dx.doi.org/10.1016/j.jacc.2025.12.014
UR - https://www.ncbi.nlm.nih.gov/pubmed/41706057
ER -