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

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

Titill: Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
Höfundur: Ntalla, Ioanna
Weng, Lu-Chen
Cartwright, James H.
Hall, Amelia Weber
Sveinbjornsson, Gardar   orcid.org/0000-0003-2429-9468
Tucker, Nathan R.
Choi, Seung Hoan
Chaffin, Mark D.
Roselli, Carolina
Barnes, Michael R.
... 177 fleiri höfundar Sýna alla höfunda
Útgáfa: 2020-05-21
Tungumál: Enska
Umfang: 2542
Háskóli/Stofnun: Háskóli Íslands
University of Iceland
Svið: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Deild: Læknadeild (HÍ)
Faculty of Medicine (UI)
Birtist í: Nature Communications;11(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-020-15706-x
Efnisorð: Multi-ancestry GWAS; Electrocardiography; Cardiovascular Diseases; Erfðarannsóknir; Arfgengi; Blóðrásarsjúkdómar
URI: https://hdl.handle.net/20.500.11815/2149

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Tilvitnun:

Ntalla, I., Weng, L., Cartwright, J.H. et al. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction. Nature Communications 11, 2542 (2020). https://doi.org/10.1038/s41467-020-15706-x

Útdráttur:

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.

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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