Abstract
Lower muscle power is related to increased risk of falls in the elderly. In sports, high power output is needed in several sprint-related disciplines. Heritability estimates for high-velocity contraction phenotypes are substantial, and recent findings related to the ACTN3 R577X polymorphism do not explain all phenotypic variability underlying this complex trait. PURPOSE: This genome-wide linkage study aimed to identify chromosomal regions linked to strength-velocity characteristics of knee muscle in young males. METHODS: A selection of 283 informative male siblings (17-36 years old), belonging to 105 families of the Leuven Genes for Muscular Strength Study, was used to conduct a genome-wide SNP-based multipoint linkage analysis(Illumina Linkage IVb 6008 SNP-panel). Strength-velocity characteristics were measured using an isokinetic dynamometer, where relative torque at 240°/s was expressed as a ratio to the relative torque at 60°/s. Also the slope of the linearized strength-velocity curve was determined. Torque-length dependency was taken as a covariate in the analyses. RESULTS: The strongest evidence for linkage was found for the strength-velocity relation of the knee extensors at 15q23 (LOD = 2.91; P < 10-4). Suggestive evidence for linkage was found at 5q34 (LOD = 2.59; P = 0.0003), 2q14.3 (LOD=2.25; P=0.0006), 4p14 (LOD=2.23; P=0.0007) and 18q23 (LOD=2.08; P=0.001). Lower LOD-scores were found for strength-velocity characteristics of the flexor musculature, with highest LOD-peak of 2.03 at 7p12.3 (P=0.001). CONCLUSIONS: Some suggestive regions for linkage were observed for strength-velocity characteristics of knee muscle. The candidate gene region at 15q23 was also linked to a specific form of inherited nemaline myopathy with additional muscle slowness phenotype. The 15q23 region harbours several candidate genes. Further fine-mapping strategies should follow to identify the candidate genes and causal gene variants. Replication of these linkage findings in larger, female and older age groups is needed. Funding: G.0496.05, G.0567.07 and PDF of the Research Foundation Flanders (FWO), OT/98/39 and OT/04/44 of the Research Fund of the K.U.Leuven.
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