Familial aggregation of atrial fibrillation in Iceland

• Published in: European Heart Journal
• Main Authors: Arnar, David O, Thorvaldsson, Sverrir, Manolio, Teri A, Thorgeirsson, Gudmundur, Kristjansson, Kristleifur, Hakonarson, Hakon, Stefansson, Kari
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press 2006
• Subjects: Aged; Atrial Fibrillation/epidemiology/*genetics; Case-Control Studies; Cohort Studies; Family Health; Female; Genetic Predisposition to Disease; Humans; Iceland/epidemiology; Male; Middle Aged; Pedigree; Risk Factors; Iceland
• Online Access: http://hdl.handle.net/2336/6508; https://doi.org/10.1093/eurheartj/ehi727

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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 KC x 100,000), 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.