TY - JOUR

T1 - Atrial fibrillation - a complex polygenetic disease

AU - Andersen, Julie H.

AU - Andreasen, Laura

AU - Olesen, Morten S.

PY - 2021

Y1 - 2021

N2 - Atrial fibrillation (AF) is the most common type of arrhythmia. Epidemiological studies have documented a substantial genetic component. More than 160 genes have been associated with AF during the last decades. Some of these were discovered by classical linkage studies while the majority relies on functional studies or genome-wide association studies. In this review, we will evaluate the genetic basis of AF and the role of both common and rare genetic variants in AF. Rare variants in multiple ion-channel genes as well as gap junction and transcription factor genes have been associated with AF. More recently, a growing body of evidence has implicated structural genes with AF. An increased burden of atrial fibrosis in AF patients compared with non-AF patients has also been reported. These findings challenge our traditional understanding of AF being an electrical disease. We will focus on several quantitative landmark papers, which are transforming our understanding of AF by implicating atrial cardiomyopathies in the pathogenesis. This new AF research field may enable better diagnostics and treatment in the future.

AB - Atrial fibrillation (AF) is the most common type of arrhythmia. Epidemiological studies have documented a substantial genetic component. More than 160 genes have been associated with AF during the last decades. Some of these were discovered by classical linkage studies while the majority relies on functional studies or genome-wide association studies. In this review, we will evaluate the genetic basis of AF and the role of both common and rare genetic variants in AF. Rare variants in multiple ion-channel genes as well as gap junction and transcription factor genes have been associated with AF. More recently, a growing body of evidence has implicated structural genes with AF. An increased burden of atrial fibrosis in AF patients compared with non-AF patients has also been reported. These findings challenge our traditional understanding of AF being an electrical disease. We will focus on several quantitative landmark papers, which are transforming our understanding of AF by implicating atrial cardiomyopathies in the pathogenesis. This new AF research field may enable better diagnostics and treatment in the future.

KW - FAMILIAL AGGREGATION

KW - SCN5A VARIANTS

KW - RARE VARIANTS

KW - GENOME-WIDE

KW - MUTATIONS

KW - RISK

KW - PREVALENCE

KW - MYOSIN

KW - COMMON

KW - HEAVY

U2 - 10.1038/s41431-020-00784-8

DO - 10.1038/s41431-020-00784-8

M3 - Journal article

C2 - 33279945

VL - 29

SP - 1051

EP - 1060

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -