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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
Hoed, Marcel den Eijgelsheim, Mark Esko, Tonu Brundel, Bianca J.J.M. Peal, David S. Evans, David M. Nolte, Ilja M. Segrè, Ayellet V. Hólm, Hilma Handsaker, Robert E.
Hoed, Marcel den
Eijgelsheim, Mark
Esko, Tonu
Brundel, Bianca J.J.M.
Peal, David S.
Evans, David M.
Nolte, Ilja M.
Segrè, Ayellet V.
Hólm, Hilma
Handsaker, Robert E.
Author
Hoed, Marcel den
Eijgelsheim, Mark
Esko, Tonu
Brundel, Bianca J.J.M.
Peal, David S.
Evans, David M.
Nolte, Ilja M.
Segrè, Ayellet V.
Hólm, Hilma
Handsaker, Robert E.
Westra, Harm-Jan
Johnson, Toby
Isaacs, Aaron
Yang, Jian
Lundby, Alicia
Zhao, Jing Hua
Kim, Young Jin
Go, Min Jin
Almgren, Peter
Bochud, Murielle
Boucher, Gabrielle
Cornalis, Marilyn C.
Gudbjartsson, Daniel F.
Hadley, David
Der Harst, Pim Van
Hayward, Caroline
Heijer, Martin den
Igl, Wilmar
Jackson, Anne U.
Lorentzon, Mattias
Eijgelsheim, Mark
Esko, Tonu
Brundel, Bianca J.J.M.
Peal, David S.
Evans, David M.
Nolte, Ilja M.
Segrè, Ayellet V.
Hólm, Hilma
Handsaker, Robert E.
Westra, Harm-Jan
Johnson, Toby
Isaacs, Aaron
Yang, Jian
Lundby, Alicia
Zhao, Jing Hua
Kim, Young Jin
Go, Min Jin
Almgren, Peter
Bochud, Murielle
Boucher, Gabrielle
Cornalis, Marilyn C.
Gudbjartsson, Daniel F.
Hadley, David
Der Harst, Pim Van
Hayward, Caroline
Heijer, Martin den
Igl, Wilmar
Jackson, Anne U.
Lorentzon, Mattias
Abstract
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.
Keywords
Date
2013
Type
Journal article
Journal
Nature Genetics
Book
Volume
45
Issue
6
Page Range
621-631
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
DOI
Source URL
Event URL
Open Access Status
License
File Access
Controlled