Genetic insights into resting heart rate and its role in cardiovascular disease.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 08 2023
02 08 2023
Historique:
received:
06
06
2022
accepted:
16
06
2023
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
2
8
2023
Statut:
epublish
Résumé
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
Identifiants
pubmed: 37532724
doi: 10.1038/s41467-023-39521-2
pii: 10.1038/s41467-023-39521-2
pmc: PMC10397318
doi:
Types de publication
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4646Subventions
Organisme : Medical Research Council
ID : MC_UU_00032/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R010676/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/7
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100114
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217065/Z/19/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212945/Z/18/Z
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK072193
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127592696
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204623/Z/16/Z
Pays : United Kingdom
Investigateurs
Delnaz Roshandel
(D)
Andrew D Paterson
(AD)
Informations de copyright
© 2023. The Author(s).
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