title: Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years.
abstract: BACKGROUND
  Three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 have been associated with atrial fibrillation (AF) in genome-wide association studies (GWAS). Five additional loci have been associated primarily with the PR interval and subsequently with AF. We aimed to investigate if 8 single nucleotide polymorphisms (SNPs), representing the 8 genomic loci previously linked with AF in genome-wide association studies, were associated with early-onset lone AF.
  
  
  METHODS
  We included 209 patients with early-onset lone AF, and a control group consisting of 534 individuals free of AF. The 8 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA).
  
  
  RESULTS
  Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004). When correcting for multiple testing, rs2200733 and rs11047543 were still significantly associated with AF.
  
  
  CONCLUSIONS
  Three SNPs, rs2200733 (4q25), rs3807989 (7p31), and rs11047543 (12p12), were associated with early-onset lone AF. All 3 SNPs are positioned close to genes that in previous studies have been demonstrated to be important for cardiac morphology/development, thereby suggesting a link between these SNPs and structural heart disease. Our results however, indicate that variants in these 3 loci are associated with AF through mechanisms that do not involve major structural abnormalities in the heart.
authors.affiliation: The Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark. morten.salling.olesen@gmail.com
authors.forename: Morten S
authors.initials: MS
authors.lastname: Olesen
authors.forename: Anders G
authors.initials: AG
authors.lastname: Holst
authors.forename: Javad
authors.initials: J
authors.lastname: Jabbari
authors.forename: Jonas B
authors.initials: JB
authors.lastname: Nielsen
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Christophersen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sajadieh
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.forename: Jesper H
authors.initials: JH
authors.lastname: Svendsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001281:Atrial Fibrillation / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult