European Heart Journal Advance Access originally published online on January 20, 2006
European Heart Journal 2006 27(6):708-712; doi:10.1093/eurheartj/ehi727
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Familial aggregation of atrial fibrillation in Iceland
1Department of Medicine, Landspitali University Hospital, Hringbraut, Reykjavik, Iceland
2deCode Genetics Inc., Sturlugata 8, 101 Reykjavik, Iceland
3National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Received 31 May 2005; revised 11 November 2005; accepted 23 December 2005; online publish-ahead-of-print 20 January 2006.
* Corresponding authors. Tel: +354 570 1900; fax: +354 570 1903. E-mail address: hakonh{at}decode.iskstefans{at}decode.is
Aims To examine the heritability of atrial fibrillation (AF) in Icelanders, utilizing a nationwide genealogy database and population-based data on AF. AF is a disorder with a high prevalence, which has been known to cluster in families, but the heritability of the common form has not been well defined.
Methods and results The study population included 5269 patients diagnosed since 1987 and age-sex-matched controls randomly selected from the genealogy database. Kinship coefficients (KC), expressed as genealogical index of familiality (GIF=average KCx100 000), were calculated before and after exclusion of relatives separated by one to five meiotic events. Risk ratios (RR) were calculated for first- to fifth-degree relatives. The average pairwise GIF among patients with AF was 15.9 (mean GIF for controls 13.9, 95%CI=13.3, 14.4); this declined to 15.4 (mean GIF for controls 13.6, 95%CI=13.1, 14.2) after exclusion of relatives separated by one meiosis and to 13.7 (mean GIF for controls 12.6, 95%CI=12.1, 13.2), 12.7 (mean GIF for controls 11.9, 95%CI=11.4, 12.4), and 11.3 (mean GIF for controls 10.6, 95%CI=10.1, 11.1) after exclusion of relatives within two, three, and four meioses, respectively (all P<0.00001). RRs among relative pairs also declined incrementally, from 1.77 in first-degree relatives to 1.36, 1.18, 1.10, and 1.05 in second- through fifth-degree relatives (all P<0.001), consistent with the declining proportion of alleles shared identically by descent. When the analysis was limited to subjects diagnosed with AF before the age of 60, first-degree relatives of the AF cases were nearly five times more likely to have AF than the general population.
Conclusion AF shows strong evidence of heritability among unselected patients in Iceland, suggesting that there may be undiscovered genetic variants underlying the risk of the common form of AF.
Key Words: Arrhythmia • Genetics • Epidemiolgy
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