Genetic Variation and Skeletal Muscle Traits: Implications for Sarcopenia

Abstract

Skeletal muscle is one of the most heritable quantitative traits studied to date, with heritability estimates ranging from 30% to 85% for muscle strength measures and 50–80% for lean mass measures. The strong genetic contribution to skeletal muscle traits indicates the possibility of using genetic approaches to individualize treatment approaches for sarcopenia or even aid in prevention strategies through the use of genetic screening prior to functional limitations. While these possibilities provide the rationale and motivation for genetic studies of skeletal muscle traits, few genes have been identified to date that appear to contribute to variation in either skeletal muscle strength or mass phenotypes, let alone sarcopenia itself. The ACE, ACTN3, CNTF, and VDR genes have been associated with skeletal muscle strength in two or more papers each, while the AR, TRHR, and VDR genes have been similarly associated with muscle mass. Only the VDR gene has been significantly associated with sarcopenia itself as an endpoint phenotype but replication of this initial finding has not yet been performed. Large-scale clinical studies relying on advanced genome-wide association techniques are needed to provide further insights into potentially clinically relevant genes that contribute to skeletal muscle traits, with identified genes then explored functionally to determine the likelihood that genetic screening can assist in the prevention and treatment of sarcopenia.