Rare genetic variants impact muscle strength.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37301943.
- Also identified by DOI 10.1038/s41467-023-39247-1 and PMC identifier 10257725.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Muscle strength is highly heritable and predictive for multiple adverse health outcomes including mortality. Here, we present a rare protein-coding variant association study in 340,319 individuals for hand grip strength, a proxy measure of muscle strength. We show that the exome-wide burden of rare protein-truncating and damaging missense variants is associated with a reduction in hand grip strength. We identify six significant hand grip strength genes, KDM5B, OBSCN, GIGYF1, TTN, RB1CC1, and EIF3J. In the example of the titin (TTN) locus we demonstrate a convergence of rare with common variant association signals and uncover genetic relationships between reduced hand grip strength and disease. Finally, we identify shared mechanisms between brain and muscle function and uncover additive effects between rare and common genetic variation on muscle strength.
Medical subject headings
- Humans
- Hand Strength
- Muscle Strength
- Muscle Strength/genetics
- Muscular Diseases
- Mutation, Missense
- Genetic Predisposition to Disease
- Carrier Proteins