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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
Journal article   Open access   Peer reviewed

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Ioanna Ntalla, Lu-Chen Weng, James H Cartwright, Amelia Weber Hall, Gardar Sveinbjornsson, Nathan R Tucker, Seung Hoan Choi, Mark D Chaffin, Carolina Roselli, Michael R Barnes, …
Nature communications, Vol.11(1), pp.2542-2542
05/21/2020
DOI: 10.1038/s41467-020-15706-x
PMCID: PMC7242331
PMID: 32439900
url
https://doi.org/10.1038/s41467-020-15706-xView
Published (Version of record) Open Access

Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Gene Expression Cardiovascular Diseases - physiopathology Genetic Predisposition to Disease - genetics Genome-Wide Association Study Endophenotypes Humans Genetic Loci - genetics Male Cardiovascular Diseases - genetics Multifactorial Inheritance Arrhythmias, Cardiac - physiopathology Genetic Variation Electrocardiography Female Arrhythmias, Cardiac - genetics Quantitative Trait Loci - genetics

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