title: Familial atrial fibrillation is a genetically heterogeneous disorder.
abstract: OBJECTIVE
  The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous.
  
  
  BACKGROUND
  Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10.
  
  
  METHODS
  Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus.
  
  
  RESULTS
  Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 +/- 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy.
  
  
  CONCLUSIONS
  Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Herron
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ballew
authors.forename: Arshad
authors.initials: A
authors.lastname: Jahangir
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Win-K
authors.initials: WK
authors.lastname: Shen
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Hammill
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Packer
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Olson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree