title: Brugada syndrome risk loci seem protective against atrial fibrillation.
abstract: Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A, and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a recent genome-wide association study (GWAS) also were associated with AF. A total of 657 patients diagnosed with AF and a control group comprising 741 individuals free of AF were included. The three SNPs were genotyped using TaqMan assays. The frequencies of risk alleles in the AF population and the control population were compared in two-by-two models. One variant, rs10428132 at SCN10A, was associated with a statistically significant decreased risk of AF (odds ratio (OR)=0.77, P=0.001). A meta-analysis was performed by enriching the control population with allele frequencies from controls in the recently published BrS GWAS (2230 alleles). In this meta-analysis, both rs10428132 at SCN10A (OR=0.73, P=5.7 × 10(-6)) and rs11708996 at SCN5A (OR=0.80, P=0.02) showed a statistically significant decreased risk of AF. When assessing the additive effect of the three loci, we found that the risk of AF decreased in a dose-responsive manner with increasing numbers of risk alleles (OR=0.50, P=0.001 for individuals carrying ≥4 risk alleles vs ≤1 allele). In conclusion, the prevalence of three risk alleles previously associated with BrS was lower in AF patients than in patients free of AF, suggesting a protective role of these loci in developing AF.
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark [3] The Ion Channel Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Laura
authors.initials: L
authors.lastname: Andreasen
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonas B
authors.initials: JB
authors.lastname: Nielsen
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Darkner
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark [3] Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Christophersen
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Javad
authors.initials: J
authors.lastname: Jabbari
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Refsgaard
authors.affiliation: Departments of Cardiothoracic Surgery and Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Thiis
authors.affiliation: Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sajadieh
authors.affiliation: Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway.
authors.forename: Arnljot
authors.initials: A
authors.lastname: Tveit
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark [3] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark [3] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper H
authors.initials: JH
authors.lastname: Svendsen
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] The Ion Channel Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitt
authors.affiliation: 1] Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark [2] Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten S
authors.initials: MS
authors.lastname: Olesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics*; D053840:Brugada Syndrome / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult