Heart failure & cardiomyopathiesCohort study
Sex and Age Specific Genetic Risk Across the Dilated and Arrhythmogenic Cardiomyopathy Spectrum
- Registry-based cohort study
- multicentre
Authors' conclusion
Gene-specific sex differences influence disease prevalence and age at onset in DCM/ACM. TTNtv are more common with earlier onset in males, whereas DSP and non-TTN sarcomeric variants predominate in females. Pediatric-onset DCM/ACM is genetically distinct and caused predominantly by non-TTN sarcomeric variants, especially during infancy.
Study context
- Population
- Genetically tested adult and pediatric dilated cardiomyopathy (DCM)/arrhythmogenic cardiomyopathy (ACM) patients and asymptomatic genotype-positive relatives in the SHaRe registry
- Participants
- 3,410 participants
- Exposure
- Females vs males with DCM/ACM
- Outcome
- Sex-based differences in genetic architecture (sex distribution across 27 DCM- and ACM-associated genes) and age at diagnosis
Main finding
As reported in the abstract
Sex distribution by genetic subtype (female vs male)
Female vs MaleOdds ratio (95% CI)P value
TTNtv
0.42(0.33–0.54)
P < 0.01DSP
3.3(2.35–4.78)
P < 0.01grouped non-TTN sarcomeric variants
1.68(1.15–2.47)
P < 0.001- Male predominance across genotype positive, genotype negative and VUS subgroups
- 61%
Observational data: associations, not effects.
Further findings
Age at diagnosis in TTNtv carriers
P = 0.003
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Pediatric-onset (diagnosis <18 years) vs adult-onset disease (subgroup, n = 174) — Pediatric-onset vs Adult-onset · non-TTN sarcomeric | 5.5 (3.3–8.9) | P < 0.01 | |
| Pediatric-onset (diagnosis <18 years) vs adult-onset disease (subgroup, n = 174) — Pediatric-onset vs Adult-onset · PKP2 | 2.8 (1.1–5.2) | P < 0.05 | |
| 0.10.31310Odds ratio (log scale) |
- Pediatric-onset (diagnosis <18 years) vs adult-onset disease (subgroup, n = 174) — Male predominance in pediatric-onset cases
- 60%
Age at diagnosis in TTNtv carriers
- Age at diagnosis comparable between sexes, except in TTNtv carriers
Pediatric-onset (diagnosis <18 years) vs adult-onset disease (subgroup, n = 174)
- Bimodal age at onset peaking in infancy and adolescence
Original publication
Sex and Age Specific Genetic Risk Across the Dilated and Arrhythmogenic Cardiomyopathy Spectrum. J Am Coll Cardiol. Published 20 May 2026. doi:10.1016/j.jacc.2026.03.054
Summarised from the published abstract; every number is checked against it