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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands.ORCID iD: 0000-0002-4934-7510
Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
St Georges Univ London, Cardiogenet Lab, Mol & Clin Sci Res Inst, London SW17 0RE, England.
Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Inst Publ Hlth Genet, Sch Publ Hlth, Seattle, WA 98195 USA.
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 2904Article in journal (Refereed) Published
Abstract [en]

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide 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 overrepresented 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 similar to 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, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

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NATURE PUBLISHING GROUP , 2018. Vol. 9, article id 2904
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Medical Genetics
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URN: urn:nbn:se:uu:diva-387268DOI: 10.1038/s41467-018-04766-9ISI: 000439687600002PubMedID: 30046033OAI: oai:DiVA.org:uu-387268DiVA, id: diva2:1331057
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AstraZenecaAvailable from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved

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