| Title: | Humans with function-disrupting variants in the myostatin gene (MSTN) have increased skeletal muscle mass and strength, and less adiposity |
| Journal: | Nature Communications |
| Published: | 13 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41826329/ |
| DOI: | https://doi.org/10.1038/s41467-026-70422-2 |
| URL: | http://dx.doi.org/10.1038/s41467-026-70422-2 |
Publication 17392
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Abstract
Myostatin negatively regulates skeletal muscle size in multiple species, and therefore, myostatin blockade has been therapeutically explored to promote muscle growth in humans, including to counter the muscle loss seen in obese humans using GLP1R agonists. In this study, we present results from a large multi-cohort genetic association analysis, using data from 1.1 million individuals to examine the effects of function-disrupting mutations in the myostatin gene (MSTN) on traits relevant to body composition and cardiometabolic health. Carriers of function-disrupting variants display decreased adiposity, an increase in lean mass, and increased grip strength and creatinine levels. We further characterize the effects of these variants on body composition using whole-body MRI data from UK Biobank, leveraging deep learning models to perform automated image segmentation for 77,572 individuals. Among mutation carriers increased muscle mass is observed across multiple muscle groups, with heterozygote carriers of loss-of-function-like mutations exhibiting increases in excess of 10%. Our findings demonstrate that lifelong reduction in myostatin function enhances muscle size and strength in humans while decreasing body adiposity, providing insights into the potential benefits and safety of long-term therapeutic blockade of myostatin signaling.</p>
20 Authors
- Joseph L. Herman
- Peter Dornbos
- Karl Landheer
- Benjamin J. Geraghty
- Marc A. Egerman
- Duc Phan
- Mary Germino
- Jason W. Mastaitis
- Johnathon R. Walls
- Luca A. Lotta
- Gonçalo Abecasis
- Aris Baras
- Judith Y. Altarejos
- Mark W. Sleeman
- Olle Melander
- Tea Shavlakadze
- George D. Yancopoulos
- Jonas Bovijn
- Jonathan Marchini
- David J. Glass
1 Application
| Application ID | Title |
|---|---|
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
Enabling scientific discoveries that improve human health