The role of common genetic variants in atrial fibrillation

Abstract

This review focuses on the genetic basis of atrial fibrillation (AF) and the role of variants in the susceptibility of developing the disease. AF is the most common cardiac arrhythmia affecting 1–2% of the general population. Studies in the last decade have demonstrated that AF, and in particular lone AF, has a substantial genetic component. A number of genome-wide association studies (GWAS) have indicated that common genetic variants, more precisely the so called single-nucleotide polymorphisms (SNPs) are associated with AF. Presently more than 10 genomic regions have been identified using this approach. Highly penetrant variants in lone AF have also been described in a number of cases. Furthermore, familial AF, although rare, have been recognized for many years.Variants associated with AF have been identified in more than 40 genes, including cardiac gap junction proteins, ion channels and beta subunits. The evidence for some of these findings is not as strong as the evidence for the common variants. All in all, it is a complex picture, as both gain- and loss of function variants have been identified in a number of the genes. This review will focus on the common variants associated with AF.The pathophysiological mechanisms responsible for AF are still far from completely understood, and it is assumed that this arrhythmia represents a complex interplay of genetic predispositions, arrhythmogenic contributors such as electrolytes and inflammatory stimuli as well as contributions from concomitant cardiac and non-cardiac diseases.