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

Ntalla, Ioanna ; Smith, Gustav LU and Munroe, Patricia B (2020) In Nature Communications 11.
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
keywords
abnormality, cardiovascular system, disease treatment, electrical method, genetic analysis, heritability, histopathology, meta-analysis, muscle
in
Nature Communications
volume
11
article number
2542
publisher
Nature Publishing Group
external identifiers
  • scopus:85085157192
  • pmid:32439900
ISSN
2041-1723
DOI
10.1038/s41467-020-15706-x
language
English
LU publication?
yes
id
0709ddc6-6e4e-4f55-8663-9d06dbca9776
date added to LUP
2020-06-15 14:31:38
date last changed
2020-12-29 01:34:32
@article{0709ddc6-6e4e-4f55-8663-9d06dbca9776,
  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.},
  author       = {Ntalla, Ioanna and Smith, Gustav and Munroe, Patricia B},
  issn         = {2041-1723},
  language     = {eng},
  month        = {05},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction},
  url          = {http://dx.doi.org/10.1038/s41467-020-15706-x},
  doi          = {10.1038/s41467-020-15706-x},
  volume       = {11},
  year         = {2020},
}