Identification of genetic variation associated with skeletal muscle histology

Skeletal muscle plays many important roles in energy metabolism and is the most abundant of the three types of muscle in humans, the others being smooth and cardiac muscle. The oxidative and glycolytic potential and the contractile properties of skeletal muscle vary considerably by fiber type, with the mitochondria-rich slow twitch fibers (Type I) having higher oxidative capacity, and fast twitch fibers (Type IIa, Type IIx and Type IIb) having higher glycolytic capacity. The proportions of skeletal muscle fiber types vary widely across a person’s body and from one person to the next. The proportions also change as people age, with Type II fibers being preferentially affected by sarcopenia. Exercising skeletal muscle is also a major metabolic sink for blood glucose and lipids. These metabolic characteristics influence elite sports performance and also affect one’s predisposition to metabolic health and disease.~45% of fiber type variance is heritable, motivativation the search for and characterization of the underlying loci. We undertook a genome-wide association study of ~650 Swedish males with histological phenotypes from skeletal muscle biopsies: four independent variants associated (P<5x10-8) with the proportion of type IIx fibers and capillary-to-fiber ratio. We are now experimentally testing the function of genes in these in relation to skeletal muscle function.