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



Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R
et al (show 177 more authors) (2020) Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction. Nature communications, 11 (1).

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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.

Item Type: Article
Uncontrolled Keywords: Cardiovascular diseases, Cardiovascular genetics, Genome-wide association studies
Depositing User: Symplectic Admin
Date Deposited: 27 May 2020 08:44
Last Modified: 18 Nov 2020 14:12
DOI: 10.1038/s41467-020-15706-x
Open Access URL: https://www.nature.com/articles/s41467-020-15706-x
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3088974