Article Text
Abstract
Background: Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque–length relationship for knee flexors and extensors.
Methods: In total, 283 informative male siblings (17–36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis.
Results: The strongest evidence for linkage was found for the torque–length relationship of the knee flexors at 14q24.3 (LOD = 4.09; p<10−5). Suggestive evidence for linkage was found at 14q32.2 (LOD = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD = 2.57; p = 0.01) for isometric knee torque at 30° flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD = 2.33, 2.69 and 2.21; p<10−4 for all) for the torque–length relationship of the knee extensors and at 18p11.31 (LOD = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque.
Conclusions: We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes.
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Footnotes
Competing interests: None.
GDM is funded by grant G.0496.05 of the Research Foundation Flanders (FWO). AW is supported by the Research Fund of the Katholieke Universiteit Leuven (OT/04/44). WH was funded by grant OT/98/39. MP is a postdoctoral Fellow (FWO). The project is funded by OT/98/39 for the phenotyping phase, and OT/04/44, G.0496.05 and mainly FWO G.0567.07 for the genome scan.