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Genome-wide linkage scan for maximal and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3
  1. Gunther De Mars (gunther.demars{at}faber.kuleuven.be)
  1. Katholieke Universiteit Leuven, Belgium
    1. An Windelinckx (an.windelinckx{at}faber.kuleuven.be)
    1. Katholieke Universiteit Leuven, Belgium
      1. Wim Huygens (wim.huygens{at}faber.kuleuven.be)
      1. Katholieke Universiteit Leuven, Belgium
        1. Maarten W Peeters (maarten.peeters{at}faber.kuleuven.be)
        1. Katholieke Universiteit Leuven, Belgium
          1. Gaston P Beunen (gaston.beunen{at}faber.kuleuven.be)
          1. Katholieke Universiteit Leuven, Belgium
            1. Jeroen Aerssens (jaerssen{at}tibbe.jnj.com)
            1. TIBOTEC, Belgium
              1. Robert Vlietinck (robert.vlietinck{at}med.kuleuven.be)
              1. Katholieke Universiteit Leuven, Belgium
                1. Martine AI Thomis (martine.thomis{at}faber.kuleuven.be)
                1. Katholieke Universiteit Leuven, Belgium

                  Abstract

                  Background: The maintenance of a 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% - 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 relation for knee flexors and extensors.

                  Methods: 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.

                  Principal findings The strongest evidence for linkage was found for the torque-length relation 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 relation 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.

                  • genetic linkage
                  • maximal strength
                  • muscle cross-sectional area
                  • torque-length relation
                  • whole genome

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