For the first time, scientists have discovered common genetic factors that influence muscle strength. The discovery offers new insights into the biology of muscle strength and its role in age-related conditions such as bone frailty.

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Researchers have recently found 16 new genetic loci that impact muscle strength.

The study, led by researchers at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge in the United Kingdom, is published in the journal Nature Communications.

The authors explain that muscle strength, as measured by hand grip strength, is widely used as a clinical indicator of muscular fitness. It is also predictive of a number of health outcomes in older people.

For example, weaker hand grip strength is a known marker of frailty and bone fracture risk, and it has been linked to lower quality of life in older adults.

It is also known that people with higher hand grip strength are more likely to recover better following surgery for hip fracture in later life.

Also, studies that have followed people over many years have shown that grip strength can predict cardiovascular disease and premature death.

The researchers note, however, that it remains unclear whether lower muscle strength actually causes these adverse outcomes or whether it is an early sign of underlying disease.

For their study, the team carried out a large-scale genetic analysis on samples from 140,000 people taking part in the UK Biobank project and from a further 50,000 people in Australia, Denmark, the Netherlands, and the U.K., all of whom were taking part in eight other studies.

They also had data on the participants’ hand grip strength and demographic, biometric, and health outcome variables.

The genetic analysis identified that muscle strength is significantly linked to 16 locations on the human genome.

Some of the 16 locations, or “loci,” are situated within or near genes already known to be important to the biology of muscles.

These genes include ACTG1, which is related to skeletal muscle fibre structure and function, and three genes called PEX14, TGFA, and SYT1, which are all important for muscle cell communication with the nervous system.

Variants of three genes identified – namely, PEX14, LRPPRC, and KANSL1 – are also known to be involved in severe muscle conditions that are caused by a single faulty gene.

The researchers believe that the findings show that the gene variants behind some severe muscle conditions may also play a role in determining muscle strength differences among people generally.

Commenting on the findings, co-senior author Dr. Robert Scott, of the MRC Epidemiology Unit, says, “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.

“These could be important steps towards identifying new treatments to prevent or treat muscle weakness.”

After establishing the link between the 16 genetic factors and muscle strength, the team then looked for clues that might show whether or not low muscle strength actually causes the health problems associated with it.

They found no evidence that reduced muscle strength directly raises risk of premature death or cardiovascular disease.

However, they did find evidence that higher muscle strength reduces risk of bone fracture.

Prof. Nick Wareham, another of the study’s senior authors and director of the MRC Epidemiology Unit, says that this finding highlights “the importance of muscle strength in the prevention of fractures and the complications which can often follow a fall.”

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.”

Co-first author Dan Wright, MRC Epidemiology Unit

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