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Original Articles

Familial Aggregation of Atrial Fibrillation

A Study in Danish Twins

Ingrid Elisabeth Christophersen, MD; Lasse Steen Ravn, MD, PhD; Esben Budtz-Joergensen, PhD; Axel Skytthe, PhD; Stig Haunsoe, MD, DMSc; Jesper Hastrup Svendsen, MD, DMSc and Kaare Christensen, MD, DMSc

From The Danish National Research Foundation Centre for Cardiac Arrhythmia (I.E.C., L.S.R., S.H., J.H.S.), Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; the Danish Twin Register, Institute of Public Health (A.S., K.C.), University of Southern Denmark, Odense, Denmark; Department of Biostatistics (E.B.-J.), University of Copenhagen, Copenhagen, Denmark; and the Department of Surgery and Medicine (S.H., H.S.), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Correspondence to Kaare Christensen, MD, J.B. Winsløws Vej 9, DK-5000 Odense C, Denmark. E-mail kchristensen{at}health.sdu.dk

Received July 1, 2008; accepted April 23, 2009.

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.

Key Words: atrial fibrillation • arrhythmia • risk factors • twin study • genetics

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CLINICAL PERSPECTIVE

Drs Christophersen and Ravn contributed equally to this work.