Arrhythmias & electrophysiologyCohort study
Cardiomyopathy-Associated Gene Variants in Atrial Fibrillation
- Prospective cohort study
- 2 cohorts (UK Biobank, All of Us)
Authors' conclusion
Results of this cohort study suggest that the prevalence of CMP-PLP variants was substantial in patients with early-onset AF. Patients with AF carrying a CMP-PLP variant had an associated increased risk of future CMP/HF, independent of clinical and polygenic risk.
Study context
- Population
- Unrelated genotyped participants with atrial fibrillation (AF), including early-onset AF, in 2 longitudinal cohorts
- Participants
- 393,768 vs 193,232
- Exposure
- CMP-PLP variant carriers vs non-carriers
- UK Biobank (UKB)n = 393,768
- AllofUsn = 193,232
- Outcome
- Prevalence of cardiomyopathy-associated pathogenic or likely pathogenic (CMP-PLP) variants and risk of incident cardiomyopathy or HF (CMP/HF) after AF diagnosis
Main finding
As reported in the abstract
CMP-PLP variant prevalence in AF; incident CMP/HF after AF diagnosis
Fold risk
1.6
95% CI 1.32–1.90
- CMP-PLP prevalence in AF, UKB
- 2.04% (95% CI, 1.89%-2.20%)
- CMP-PLP prevalence in AF, AllofUs
- 2.52% (95% CI, 2.25%-2.82%)
- CMP-PLP prevalence in AF onset <45 y, UKB
- 4.99% (95% CI, 3.07%-7.91%)
- CMP-PLP prevalence in AF onset <45 y, AllofUs
- 4.66% (3.40%-6.32%)
Observational data: associations, not effects.
Further findings
| Outcome | UKB | AllofUs |
|---|---|---|
| Prevalence of CMP-PLP variants in AF with onset before age 45 years | 4.99% (95% CI 3.07%–7.91%) | 4.66% (95% CI 3.40%–6.32%) |
Prevalence of CMP-PLP variants in AF with onset before age 45 years
- 5 times as prevalent as in the biobank populations
Cumulative incidence of CMP/HF
- AF
- 18%
- No AF
- 3%
Joint contributions to CMP/HF
- CMP-PLP variants, a polygenic score and clinical risk factors were independent estimators of CMP/HF
Original publication
Cardiomyopathy-Associated Gene Variants in Atrial Fibrillation. JAMA Cardiol. Published 1 June 2025. doi:10.1001/jamacardio.2025.0460
Summarised from the published abstract; every number is checked against it