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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-8081-428X
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2013 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 6, p. 621-+Article in journal (Refereed) Published
Abstract [en]

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Place, publisher, year, edition, pages
2013. Vol. 45, no 6, p. 621-+
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-203280DOI: 10.1038/ng.2610ISI: 000319563900009OAI: oai:DiVA.org:uu-203280DiVA, id: diva2:636231
Available from: 2013-07-09 Created: 2013-07-08 Last updated: 2017-12-06Bibliographically approved

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den Hoed, MarcelJohansson, AsaIngelsson, ErikLind, LarsGyllensten, Ulf
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Department of Medical SciencesScience for Life Laboratory, SciLifeLabDepartment of Immunology, Genetics and PathologyGenomicsUCR-Uppsala Clinical Research CenterCardiovascular epidemiology
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