Heart failure & cardiomyopathiesCross-sectional study
Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies
- Cross-sectional study
Authors' conclusion
The findings in this study indicate that HCM and DCM risk were modified by polygenic background, which exists on an overlapping but opposing spectrum.
Study context
- Population
- Penn Medicine BioBank participants with EHR and genotyping data
- Participants
- 49,434 participants
- Exposure
- HCM and DCM polygenic scores and pathogenic variant carrier status
- Outcome
- HCM and DCM defined by EHR diagnosis and procedure codes, and echocardiogram measurements
Main finding
As reported in the abstract
Odds ratio (95% CI)P value
HCM PGS (per 1-SD increase)risk of HCM
1.8(1.6–2.0)
P = 9.6 × 10-25HCM PGS (per 1-SD increase)risk of DCM
0.69(0.64–0.74)
P = 4.3 × 10-22DCM PGS (per 1-SD increase)risk of DCM
1.6(1.5–1.7)
P = 1.7 × 10-40DCM PGS (per 1-SD increase)risk of HCM
0.69(0.63–0.76)
P = 3.0 × 10-13Per 1-SD increase, as printed
Observational data: associations, not effects.
Further findings
Echocardiographic measures, HCM PGS
| Comparison | increase (%) (95% CI) | P value | |
|---|---|---|---|
| HCM PGS (increase) · LVEF | 1.1 (0.9–1.3) | P = 7.3 × 10-31 | |
| −1012Difference, % (linear scale) |
Echocardiographic measures, HCM PGS
| Comparison | increase (mm) (95% CI) | P value | |
|---|---|---|---|
| HCM PGS (increase) · IVS thickness | 0.18 (0.14–0.22) | P = 9.3 × 10-19 | |
| −0.100.10.20.3Difference, mm (linear scale) |
| Outcome | increase (mm) (95% CI) | P value | |
|---|---|---|---|
| Echocardiographic measures, DCM PGS (per 1-SD increase) — DCM PGS (per 1-SD increase) · LVIDd | 1.0 (0.93–1.1) | P = 3.2 × 10-78 | |
| −0.500.511.5Difference, mm (linear scale) |
| Outcome | Estimate | P value |
|---|---|---|
| Echocardiographic measures, HCM PGS — HCM PGS (increase) · LVIDd | decrease 0.79 mm (95% CI −0.92 to −0.67) | P = 2.3 × 10-36 |
| Echocardiographic measures, DCM PGS (per 1-SD increase) — DCM PGS (per 1-SD increase) · LVEF | decrease 2.0 % (95% CI −2.2 to −1.8) | P = 3.3 × 10-83 |
| Echocardiographic measures, DCM PGS (per 1-SD increase) — DCM PGS (per 1-SD increase) · IVS; not significant | estimate −1.3 × 10⁻3 mm (95% CI −0.04 to 0.03) | P = 0.94 |
| Discrimination (AUC) gain from adding HCM or DCM PGS to age, sex and monogenic variant status — Model with PGS vs Model with age, sex, monogenic status · HCM; CrI | AUC improvement 0.043 (95% CI 0.034–0.053) | |
| Discrimination (AUC) gain from adding HCM or DCM PGS to age, sex and monogenic variant status — Model with PGS vs Model with age, sex, monogenic status · DCM; CrI | AUC improvement 0.045 (95% CrI 0.039–0.051) |
Discrimination (AUC) gain from adding HCM or DCM PGS to age, sex and monogenic variant status
- Monogenic and polygenic risk terms had significant independent effects in combined models
Original publication
Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies. JAMA Cardiol. Published 1 February 2026. doi:10.1001/jamacardio.2025.4739
Summarised from the published abstract; every number is checked against it