TY - JOUR

T1 - Familial aggregation of atrial fibrillation: a study in Danish twins

AU - Christophersen, Ingrid Elisabeth

AU - Ravn, Lasse Steen

AU - Budtz-Joergensen, Esben

AU - Skytthe, Axel

AU - Haunsoe, Stig

AU - Svendsen, Jesper Hastrup

AU - Christensen, Kaare

N1 - Keywords: Aged; Aged, 80 and over; Atrial Fibrillation; Biometry; Denmark; Family Health; Female; Humans; Incidence; Male; Middle Aged; Models, Genetic; Prevalence; Proportional Hazards Models; Registries; Risk Factors; Twins, Dizygotic; Twins, Monozygotic

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Heritability may play a role in nonfamilial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared with a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) in which one or both members were diagnosed with AF were identified in The Danish Twin Registry. Concordance rates were twice as high for MZ pairs than for DZ pairs regardless of sex (22.0% versus 11.6%, P<0.0001). In a Cox regression of event-free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event-free survival time (hazard ratio, 2.0; 95% CI, 1.3 to 3.0), thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62% (55% to 68%), due to additive genetics. There were no significant differences across sexes. CONCLUSIONS: All the analyses of twin similarities in the present study indicate that genetic factors play a substantial role in the risk of AF for both sexes. The recurrence risk for co-twins (12% to 22%) is clinically relevant and suggests that co-twins of AF-affected twins belong to a high-risk group for AF.

AB - BACKGROUND: Heritability may play a role in nonfamilial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared with a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) in which one or both members were diagnosed with AF were identified in The Danish Twin Registry. Concordance rates were twice as high for MZ pairs than for DZ pairs regardless of sex (22.0% versus 11.6%, P<0.0001). In a Cox regression of event-free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event-free survival time (hazard ratio, 2.0; 95% CI, 1.3 to 3.0), thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62% (55% to 68%), due to additive genetics. There were no significant differences across sexes. CONCLUSIONS: All the analyses of twin similarities in the present study indicate that genetic factors play a substantial role in the risk of AF for both sexes. The recurrence risk for co-twins (12% to 22%) is clinically relevant and suggests that co-twins of AF-affected twins belong to a high-risk group for AF.

U2 - 10.1161/CIRCEP.108.786665

DO - 10.1161/CIRCEP.108.786665

M3 - Journal article

C2 - 19808493

VL - 2

SP - 378

EP - 383

JO - Circulation: Arrhythmia and Electrophysiology

JF - Circulation: Arrhythmia and Electrophysiology

SN - 1941-3149

IS - 4

ER -