Heart failure & cardiomyopathies
Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3
Authors' conclusion
BAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN-mediated DCM.
Study context
- Population
- Individuals of European and African genetic ancestry in the Penn Medicine BioBank with whole-exome sequencing (WES) linked to electronic health record (EHR) phenotypes, 2014–2023PMBB
- Participants
- 43,731 individuals
- Exposure
- BAG3 C151R carriers vs noncarriers
- Outcome
- Association of BAG3 coding variation with clinical diagnoses, echocardiographic traits and longitudinal outcomes
Methodological detailshealth care population-based, replication cohorts
- Health care population-based
- Replication cohorts
Main finding
As reported in the abstract
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) risk with C151R
Carriers vs NoncarriersOdds ratio (95% CI)
DCM
0.85(0.78–0.92)
HCM
1.59(1.25–2.02)
Observational data: associations, not effects.
Further findings
Median
| Outcome | Carriers | Noncarriers | Estimate | |
|---|---|---|---|---|
| Age at death | 71.8 (IQR 63.1–80.7) | 70.3 (IQR 61.6–79.2) | HR 0.85 (95% CI 0.74–0.96) | |
| Heart transplant · median age at transplant | 56.7 (IQR 46.1–63.1) | 55.6 (IQR 45.2–62.9) | HR 0.81 (95% CI 0.66–0.99) | |
| DCM and HF among truncating TTN variant carriers (subgroup, n = 358) · DCM | OR 0.42 (95% CI 0.24–0.74) | |||
| DCM and HF among truncating TTN variant carriers (subgroup, n = 358) · HF | OR 0.27 (95% CI 0.14–0.50) | |||
| 0.10.31310Ratio (log scale) |
Original publication
Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3. JAMA Cardiol. Published 1 December 2024. doi:10.
Summarised from the published abstract; every number is checked against it