Gene-environmental interaction for common arrhythmias based on GWAS data

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Understanding of arrhythmias has been substantially advanced by gene mutation analysis in familiar arrhythmia syndromes and studies of ionic channels with the patch-clamp technique in cell-level. The remaining major problem in arrhythmia research is the understanding and therapeutic strategy for atrial and ventricular fibrillation. On the other hand, genome-wide-association study (GWAS) is a comprehensive, un-biased approach and could reveal novel pathways leading to diseases. Thus, we performed biological functional analysis for genes that had been newly identified in GWAS of atrial and ventricular fibrillation. In atrial fibrillation, we found one strong genetic risk related to trigger mechanism, and multiple weak genetic risks related to maintenance mechanism. In ventricular fibrillation, we found that a defective transcription factor expressed in the His-Purkinje system causes exercise-induced idiopathic ventricular fibrillation.