In a genome-wide association study, researchers from the University of Cambridge and elsewhere have identified 16 common genetic variants which influence muscle strength in humans. The results appear today in the journal Nature Communications.
Willems et al identified 16 genetic variants associated with maximal hand grip strength. Image credit: Skeeze.
“This work highlights the importance of muscle strength in the prevention of fractures and the complications which can often follow a fall,” said senior author Professor Nick Wareham, from the University of Cambridge School of Clinical Medicine.
Professor Wareham and colleagues used data on hand grip strength from 142,035 participants in the UK Biobank study, combined with 53,145 additional individuals from the UK, Netherlands, Denmark and Australia.
“The very large number of individuals participating in UK Biobank provides a powerful resource for identifying genes involved in complex traits such as muscle strength, and helps us understand their underlying biology and its relevance to health,” said first author Dan Wright, a PhD student at the Medical Research Council Epidemiology Unit at the University of Cambridge.
The researchers identified 16 genome-wide significant variants associated with grip strength — within or near POLD3, TGFA, ERP27, HOXB3, GLIS1, PEX14, MGMT, LRPPRC, SYT1, GBF1, KANSL1, SLC8A1, IGSF9B, ACTG1, DEC1 and HLA.
Many of the genes highlighted are known to play a role in biological processes highly relevant to muscle function, including the structure and function of muscle fibres (ACTG1), and the communication of the nervous system with muscle cells (SYT1).
Mutations in some of these genes are also known to be associated with severe monogenic syndromes — conditions caused by a single genetic mutation — characterised by compromised muscle function.
This demonstrates that genetic variation in genes which cause serious muscular conditions may also influence differences in strength in the general population.
“While we have long suspected a role for genetics in the variation in muscle strength, these findings give the first insights into some of the specific genetic variants that underpin variation in strength,” said co-lead author Dr. Robert Scott, also from the Medical Research Council Epidemiology Unit at the University of Cambridge.
“These could be important steps towards identifying new treatments to prevent or treat muscle weakness.”
Using the 16 genetic variants identified, the authors were able to investigate the hypothesised causal link between strength and these adverse health outcomes.
The study found no evidence that lower strength causally increases risk of death or cardiovascular disease, but they did find evidence that higher muscular strength reduces risk of fracture, supporting the use of strength training interventions as a strategy to reduce risk of fractures.
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Sara M. Willems et al. 2017. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications 8, article number: 16015; doi: 10.1038/ncomms16015
