Genetic insights into resting heart rate and its role in cardiovascular disease
van de Vegte, Y.J. ; Ladenvall, C. LU ; Melander, O. LU
; Groop, L.
LU
; Smith, J.G.
LU
and van der Harst, P.
(2023)
In Nature Communications
14(1).
- Abstract
- 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... (More)
- 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. © 2023, The Author(s). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/6653cb99-7941-43e3-981d-3542e491f8e0
- author
- van de Vegte, Y.J.
; Ladenvall, C.
LU
; Melander, O.
LU
; Groop, L.
LU
; Smith, J.G.
LU
and van der Harst, P.
- author collaboration
- organization
-
- Translational Muscle Research (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- Cardiovascular Research - Hypertension (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Heart Failure and Mechanical Support (research group)
- Cardiovascular Epigenetics (research group)
- Cardiology
- Molecular Epidemiology and Cardiology (research group)
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Atrial Fibrillation, Cardiovascular Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Rate, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, cardiovascular disease, cardiovascular system, meta-analysis, mortality, sampling, atrial fibrillation, genetic predisposition, genetics, genome-wide association study, heart rate, human, Mendelian randomization analysis, meta analysis, procedures, risk factor, single nucleotide polymorphism
- in
- Nature Communications
- volume
- 14
- issue
- 1
- article number
- 4646
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85166440619
- pmid:37532724
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-023-39521-2
- language
- English
- LU publication?
- yes
- id
- 6653cb99-7941-43e3-981d-3542e491f8e0
- date added to LUP
- 2023-11-24 16:26:45
- date last changed
- 2024-04-07 16:42:16
@article{6653cb99-7941-43e3-981d-3542e491f8e0,
abstract = {{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. © 2023, The Author(s).}},
author = {{van de Vegte, Y.J. and Ladenvall, C. and Melander, O. and Groop, L. and Smith, J.G. and van der Harst, P.}},
issn = {{2041-1723}},
keywords = {{Atrial Fibrillation; Cardiovascular Diseases; Genetic Predisposition to Disease; Genome-Wide Association Study; Heart Rate; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; cardiovascular disease; cardiovascular system; meta-analysis; mortality; sampling; atrial fibrillation; genetic predisposition; genetics; genome-wide association study; heart rate; human; Mendelian randomization analysis; meta analysis; procedures; risk factor; single nucleotide polymorphism}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Genetic insights into resting heart rate and its role in cardiovascular disease}},
url = {{http://dx.doi.org/10.1038/s41467-023-39521-2}},
doi = {{10.1038/s41467-023-39521-2}},
volume = {{14}},
year = {{2023}},
}