Causal associations between cardiorespiratory fitness and type 2 diabetes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 07 2023
03 07 2023
Historique:
received:
06
05
2022
accepted:
21
04
2023
medline:
5
7
2023
pubmed:
4
7
2023
entrez:
3
7
2023
Statut:
epublish
Résumé
Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention.
Identifiants
pubmed: 37400433
doi: 10.1038/s41467-023-38234-w
pii: 10.1038/s41467-023-38234-w
pmc: PMC10318084
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3904Subventions
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/4
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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