title: Familial aggregation of atrial fibrillation in Iceland.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Landspitali University Hospital, Hringbraut, Reykjavik, Iceland.
authors.forename: David O
authors.initials: DO
authors.lastname: Arnar
authors.forename: Sverrir
authors.initials: S
authors.lastname: Thorvaldsson
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjansson
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors