title: Association of atrial fibrillation susceptibility genes, atrial fibrillation phenotypes and response to catheter ablation: a gene-based analysis of GWAS data.
abstract: Previous studies have suggested PITX2, KCNN3 and ZFHX3 as atrial fibrillation (AF) susceptibility genes. Single common genetic polymorphisms of those genes have been linked with AF phenotypes and rhythm outcome of AF catheter ablation although their mechanisms remain elusive. New gene-based association tests may help clarifying genotype-phenotype correlations. Therefore, we hypothesized that PITX2, KCNN3 and ZFHX3 associate with left atrial enlargement and persistent AF and subsequently with ablation outcome.
  
  
  
  Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using two different gene-based association tests (VEGAS, minSNP). Among the three candidate genes, only ZFHX3 associated with left atrial dilatation and AF recurrence after catheter ablation.
  
  
  
  This study suggests a contribution of ZFHX3 to AF remodeling and response to therapy. Future and larger studies are necessary to replicate and apply these findings with an emphasis on designing AF pathophysiology-based multi-locus risk scores.
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany. dani11@gmx.net.
authors.forename: Daniela
authors.initials: D
authors.lastname: Husser
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Büttner
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Ueberham
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Borislav
authors.initials: B
authors.lastname: Dinov
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Sommer
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Arya
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hindricks
authors.affiliation: Department of Electrophysiology, Heart Center Leipzig, Leipzig University, Strümpellstr. 39, 04289, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bollmann
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics* / Q000601:surgery*; D017115:Catheter Ablation; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence
keywords: Atrial fibrillation; Catheter ablation; Gene-based analysis; Genome wide association study