| Title: |
Causal associations between cardiorespiratory fitness and type 2 diabetes |
| Authors: |
Cai, L; Gonzales, T; Wheeler, E; Kerrison, ND; Day, FR; Langenberg, C; Perry, JRB; Brage, S; Wareham, NJ |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2023 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
NATURE COMMUNICATIONS; https://qmro.qmul.ac.uk/xmlui/handle/123456789/103596 |
| DOI: |
10.1038/s41467-023-38234-w |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/103596; https://doi.org/10.1038/s41467-023-38234-w |
| Rights: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. ; © The Author(s) 2023 |
| Accession Number: |
edsbas.55841A0D |
| Database: |
BASE |