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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity


Title: PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Author: van Setten, Jessica
Brody, Jennifer A.
Jamshidi, Yalda
Swenson, Brenton R.
Butler, Anne M.
Campbell, Harry
Del Greco, Fabiola M.
Evans, Daniel S.
Gibson, Quince
Gudbjartsson, Daniel   orcid.org/0000-0002-5222-9857
... 116 more authors Show all authors
Date: 2018-07-25
Language: English
Scope: 2904
University/Institute: Háskóli Íslands (HÍ)
University of Iceland (UI)
School: School of Engineering and Natural Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
School of Health Sciences (UI)
Heilbrigðisvísindasvið (HÍ)
Department: Faculty of Medicine (UI)
Læknadeild (HÍ)
Series: Nature Communications;9(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-018-04766-9
Subject: Atrial Fibrillation; Heart Diseases; Heart Block; Genome-Wide Association Study; Cardiovascular genetics
URI: https://hdl.handle.net/20.500.11815/1392

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Citation:

van Setten, J., Brody, J.A., Jamshidi, Y. et al. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity. Nat Commun 9, 2904 (2018) doi:10.1038/s41467-018-04766-9

Abstract:

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

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