@article{Stroeks:2026:10.1016/j.jacc.2026.03.054,
author = {Stroeks, SLVM and Bart, NK and Rossano, J and Claggett, B and Beelen, NJ and Buchan, RJ and Day, S and Fornaro, A and Halliday, BP and Wheeler, MT and Hammersley, DJ and Helms, A and Heymans, ABM and Ho, CY and Khan, SS and Lin, K and Lota, A and Merlo, M and Mestroni, L and Olivotto, I and Owens, A and Seidman, CE and Shore, S and Sinnette, C and Sinagra, G and Stevenson, LW and Stewart, GC and Theotakis, P and Venner, MFGHM and Ware, JS and Taylor, MRG and Verdonschot, JAJ and Wilsbacher, L and Prasad, S and Heymans, SR and Parikh, VN and Tayal, U and Lakdawala, NK and DCMACM, SHaRe Investigators},
doi = {10.1016/j.jacc.2026.03.054},
journal = {Journal of the American College of Cardiology},
pages = {3573--3588},
title = {Sex and age specific genetic risk across the dilated and arrhythmogenic cardiomyopathy spectrum: insights from the SHaRe registry},
url = {http://dx.doi.org/10.1016/j.jacc.2026.03.054},
volume = {87},
year = {2026}
}

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TY  - JOUR
AB  - BackgroundDilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) are progressive cardiac muscle disorders with phenotypic and genetic overlap. Although a male predominance is noted in DCM/ACM, it remains unclear whether this extends to specific genetic subtypes or reflects variation in disease stage and whether sex influences age-dependent disease onset across pediatric and adult groups.ObjectivesThe aim of this study was to define sex-based differences in genetic architecture and age at diagnosis of DCM/ACM across pediatric and adult populations.MethodsGenetically tested adult and pediatric DCM/ACM patients and asymptomatic genotype-positive relatives enrolled in the multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Sex distribution across 27 DCM- and ACM-associated genes was evaluated using logistic regression. Age at diagnosis was compared across sex and genes using Kaplan-Meier cumulative incidence estimates.ResultsAmong 3,410 patients, a 61% male predominance was present across subgroups of genotype positive, genotype negative, and variants of uncertain significance (P = 0.008), with significant gene-specific variation. TTN truncating variants (TTNtv) were less common in females (OR: 0.42 [95% CI: 0.33-0.54]; P < 0.01), while DSP (OR: 3.3 [95% CI: 2.35-4.78]; P < 0.01) and grouped non-TTN sarcomeric variants (ACTC1, TNNT2, MYH7, TNNC1, TNNI3, and TPM1) were more common (OR: 1.68 [95% CI: 1.15-2.47]; P < 0.001) in females compared with males with DCM/ACM. Age at diagnosis was comparable between sexes, except in TTNtv carriers, among whom males exhibited earlier disease onset compared with females (median age 45 years [Q1-Q3: 33-55 years] vs 51 years [Q1-Q3: 38-60 years]; P = 0.003). Pediatric-onset (diagnosis at <18 years) cases (n = 174) also demonstrated a male predominance (60% male) but had distinct genetic characteristics, with non-TTN sarcomeric and PKP2 variants being more prevalent compared with adult-o
AU  - Stroeks,SLVM
AU  - Bart,NK
AU  - Rossano,J
AU  - Claggett,B
AU  - Beelen,NJ
AU  - Buchan,RJ
AU  - Day,S
AU  - Fornaro,A
AU  - Halliday,BP
AU  - Wheeler,MT
AU  - Hammersley,DJ
AU  - Helms,A
AU  - Heymans,ABM
AU  - Ho,CY
AU  - Khan,SS
AU  - Lin,K
AU  - Lota,A
AU  - Merlo,M
AU  - Mestroni,L
AU  - Olivotto,I
AU  - Owens,A
AU  - Seidman,CE
AU  - Shore,S
AU  - Sinnette,C
AU  - Sinagra,G
AU  - Stevenson,LW
AU  - Stewart,GC
AU  - Theotakis,P
AU  - Venner,MFGHM
AU  - Ware,JS
AU  - Taylor,MRG
AU  - Verdonschot,JAJ
AU  - Wilsbacher,L
AU  - Prasad,S
AU  - Heymans,SR
AU  - Parikh,VN
AU  - Tayal,U
AU  - Lakdawala,NK
AU  - DCMACM,SHaRe Investigators
DO  - 10.1016/j.jacc.2026.03.054
EP  - 3588
PY  - 2026///
SN  - 0735-1097
SP  - 3573
TI  - Sex and age specific genetic risk across the dilated and arrhythmogenic cardiomyopathy spectrum: insights from the SHaRe registry
T2  - Journal of the American College of Cardiology
UR  - http://dx.doi.org/10.1016/j.jacc.2026.03.054
VL  - 87
ER  - 

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