Arrhythmias & electrophysiologyCohort study
Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation
- Prospective cohort study
- whole-genome sequencing
- UK Biobank
Authors' conclusion
Results of this cohort study demonstrated the complementary value of common, rare, and somatic variants in shaping genomic AF risk.
Study context
- Population
- UK Biobank participants aged 40 to 69 years, recruited in the UK 2006–201030,797 atrial fibrillation (AF) cases
- Participants
- 416,085 participants
- Exposure
- Polygenic, monogenic and somatic genetic variants and incident AF
- Outcome
- Hazard ratios (HRs) for incident AF attributable to polygenic risk score (PRS), AFgeneset, clonal hematopoiesis of indeterminate potential (CHIP) and their interactions
- Follow-up
- 5-year
Main finding
As reported in the abstract
Incident AF
Hazard ratio (95% CI)P value
PRSper 1 SD
1.65(1.63–1.67)
P < 1 × 10-8AFgeneset
1.63(1.52–1.75)
P = 1.46 × 10-42CHIP
1.26(1.15–1.38)
P = 1.41 × 10-6Per 1 SD, as printed
Observational data: associations, not effects.
Further findings
Prediction: IGM-AF integrated with Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF)
- C statistic, IGM-AF + CHARGE-AF (higher than IGM-AF or CHARGE-AF alone)
- 0.80 (95% CI, 0.80-0.80)
- Net reclassification index, IGM-AF added to CHARGE-AF
- 0.08 (95% CI, 0.07-0.09)
Original publication
Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation. JAMA Cardiol. Published 1 December 2025. doi:10.1001/jamacardio.2025.3664
Summarised from the published abstract; every number is checked against it