Genetics of Atrial Fibrillation: State of the Art in 2017.

ABSTRACT

Genetic variation is an important determinant of atrial fibrillation (AF) susceptibility. Numerous rare variants in protein-coding sequences of genes have been associated with AF in families and in early-onset cases, and chromosomal loci harbouring common risk variants have been mapped in AF cohorts. Many of these loci are in non-coding regions of the human genome and are thought to contain regulatory sequences that modulate gene expression. Disease genes implicated to date have predominantly encoded cardiac ion channels, with predicted mutation effects on the atrial action potential duration. More recent studies have expanded the spectrum of disease-associated genes to include myocardial structural components and have highlighted an unsuspected role for cardiac transcription factors. These paradigm-shifting discoveries suggest that abnormalities of atrial specification arising during cardiac development might provide a template for AF in later adult life. With the escalating pace of variant discovery, there is an increasing need for mechanistic studies not only to evaluate single variants, but also to determine the collective effects of each person's burden of rare and common genetic variants, co-morbidities and lifestyle factors on the atrial substrate for arrhythmogenesis. Elucidation of an individual's genetic predisposition and modifiable environmental risk factors will facilitate personalised approaches to AF treatment.