Loss-of-Function Variants in the SYNPO2L Gene Are Associated With Atrial Fibrillation

Frontiers in Cardiovascular Medicine

Julie Husted Andersen¹  Oliver Bundgaard Vad¹  Alexander Guldmann Clausen¹  Morten Salling Olesen² 

[1] Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;

关键词: atrial fibrillation;    genetics;    arrhythmia;    splice site variant;    cardiomyopathy;    cardiology;   

DOI  :  10.3389/fcvm.2021.650667

来源: Frontiers

【 摘 要 】

Multiple genome-wide association studies (GWAS) have identified numerous loci associated with atrial fibrillation (AF). However, the genes driving these associations and how they contribute to the AF pathogenesis remains poorly understood. To identify genes likely to be driving the observed association, we searched the FinnGen study consisting of 12,859 AF cases and 73,341 controls for rare genetic variants predicted to cause loss-of-function. A specific splice site variant was found in the SYNPO2L gene, located in an AF associated locus on chromosome 10. This variant was associated with an increased risk of AF with a relatively high odds ratio of 3.5 (p = 9.9 × 10−8). SYNPO2L is an important gene involved in the structural development and function of the cardiac myocyte and our findings thus support the recent suggestions that AF can present as atrial cardiomyopathy.

【 授权许可】

CC BY