Genome-wide linkage scan for resistance to muscle fatigue

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Resistance to muscle fatigue depends on age, sex, muscle fiber type, activation by the nervous system and training. Heritability of muscle strength phenotypes ranges between 31% and 78%, although little is known about heritability of muscle fatigue. A first aim of this study was to estimate the heritability for fatigue resistance after a short bout of intense exercise of the knee musculature. The main purpose was to identify chromosomal regions linked to muscle fatigue applying genome-wide linkage analyses. A selection of 283 informative male siblings (17-36 years old), belonging to 105 families, was used to conduct a genome-wide SNP-based multipoint linkage analysis. Heritabilities for resistance to muscle fatigue ranged from 21% to 54%. The strongest linkage signal was found at 19q13.11 (LOD=2.158; P<0.0001) and at 1q32.1 (LOD=2.142; P<0.0001) for resistance to fatigue of the knee flexors; however, no marker reached genome-wide significance. Several other regions with LOD>1.5 were found (1p31.3, 3q29, 8p22, 11q25 and 19q12). When replicated in an independent sample, these results warrant further fine mapping studies aiming to detect genes that underlie variation in muscle fatigue.