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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
Dalarna University, School of Education, Health and Social Studies, Medical Science.ORCID iD: 0000-0002-6933-4637
Number of Authors: 230
2014 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, 826-836 p.Article in journal (Refereed) Published
Abstract [en]

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Place, publisher, year, edition, pages
2014. Vol. 46, 826-836 p.
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-21326DOI: 10.1038/ng.3014ISI: 000339704400010PubMedID: 24952745OAI: oai:DiVA.org:du-21326DiVA: diva2:916842
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2016-04-05Bibliographically approved

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