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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Translational Medicine 1/2017

Association of atrial fibrillation susceptibility genes, atrial fibrillation phenotypes and response to catheter ablation: a gene-based analysis of GWAS data

Journal of Translational Medicine > Ausgabe 1/2017
Daniela Husser, Petra Büttner, Laura Ueberham, Borislav Dinov, Philipp Sommer, Arash Arya, Gerhard Hindricks, Andreas Bollmann
Wichtige Hinweise
Daniela Husser and Petra Büttner contributed equally to this work



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.

Methods and results

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.
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