Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
Journal article
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, ... Lorentzon, Mattias. (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics. 45(6), pp. 621 - 631. https://doi.org/10.1038/ng.2610
Authors | 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. and 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. |
Year | 2013 |
Journal | Nature Genetics |
Journal citation | 45 (6), pp. 621 - 631 |
Publisher | Nature Publishing Group |
ISSN | 1061-4036 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/ng.2610 |
Scopus EID | 2-s2.0-84878726099 |
Page range | 621 - 631 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/85846/identification-of-heart-rate-associated-loci-and-their-effects-on-cardiac-conduction-and-rhythm-disorders
Restricted files
Publisher's version
78
total views0
total downloads2
views this month0
downloads this month