Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study

Abstract

De Mars G, Windelinckx A, Huygens W, Peeters MW, Beunen GP, Aerssens J, Vlietinck R, Thomis MA. Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study. Physiol Genomics 35: 36 -44, 2008. First published August 5, 2008 doi:10.1152/physiolgenomics.90252.2008.-The torque-velocity relationship is known to be affected by ageing, decreasing its protective role in the prevention of falls. Interindividual variability in this torque-velocity relationship is partly determined by genetic factors (h 2 : 44 -67%). As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to the torque-velocity relationship of the knee flexors and extensors. A selection of 283 informative male siblings (17-36 yr), belonging to 105 families, was used to conduct a genome-wide SNP-based (Illumina Linkage IVb panel) multipoint linkage analysis for the torque-velocity relationship of the knee flexors and extensors. The strongest evidence for linkage was found at 15q23 for the torque-velocity slope of the knee extensors (TVSE). Other interesting linkage regions with LOD scores Ͼ2 were found at 7p12.3 [logarithm of the odds ratio (LOD) ϭ 2.03, P ϭ 0.0011] for the torque-velocity ratio of the knee flexors (TVRF), at 2q14.3 (LOD ϭ 2.25, P ϭ 0.0006) for TVSE, and at 4p14 and 18q23 for the torque-velocity ratio of the knee extensors TVRE (LOD ϭ 2.23 and 2.08; P ϭ 0.0007 and 0.001, respectively). We conclude that many small contributing genes are involved in causing variation in the torque-velocity relationship of the knee flexor and extensor muscles. Several earlier reported candidate genes for muscle strength and muscle mass and new candidates are harbored within or in close vicinity of the linkage regions reported in the present study.human muscle strength; torque-velocity relationship; linkage; whole genome THE FORCE GENERATED BY A MUSCLE not only depends on the length of the muscle, and thus the sarcomere length or contractile filaments overlap, but it also varies with the velocity at which it shortens. With increasing shortening velocity, the force sustained by the muscle rapidly decreases, finally leading to a velocity at which force can no longer be sustained; this is the maximum velocity of shortening (V max ). Force at zero velocity of shortening is the isometric force (F 0 ). It is possible to compare muscles of different sizes by expressing the force at a particular velocity as a fraction of F 0 . The speed of shortening of a contracting muscle is dependent on the number of sarcomeres in series.The torque-velocity relationship is known to be affected by ageing (6,34,44), and concentric torques have been found to be depressed in older individuals (15, 24). The deficit in concentric peak torque between young and elderly individuals has also been found to increase with contraction velocity (6). Explosive muscle power (the product of force and the speed at which force is produced during the first seconds of a movement) is importa...

Association between polymorphisms in the TRHR gene, fat-free mass, and muscle strength in older women

“…However, the differences observed in the present study were modest when considering the high heritability of musclerelated phenotypes (Liu et al 2009;De Mars et al 2008). Probably, many genes with small contributions, rather than few genes with strong influence, are expected to determine the interindividual differences of such traits (Thompson et al 2004;De Mars et al 2008;Pescatello et al 2006). Thus, the present study provides evidence that the studied polymorphism (rs16892496) in the TRHR gene is one genetic variant AFFM appendicular fat-free mass, PT peak torque AGE (2013AGE ( ) 35:2477AGE ( -2483that contributes to FFM and muscle strength in crosssectional analyses, though its clinical relevance remains to be investigated.…”

“…It was observed that the C allele carriers were more likely to be classified in the lower quartile of muscle strength. However, the differences observed in the present study were modest when considering the high heritability of musclerelated phenotypes (Liu et al 2009;De Mars et al 2008). Probably, many genes with small contributions, rather than few genes with strong influence, are expected to determine the interindividual differences of such traits (Thompson et al 2004;De Mars et al 2008;Pescatello et al 2006).…”

“…De Mars et al (2008) sought to identify chromosomal regions linked to muscle area and bone cross-sectional, knee flexors, and extensors isometric torque in twins. The authors concluded that many genes still have little explanation for muscle strength determination (De Mars et al 2008).…”

“…De Mars et al (2008) sought to identify chromosomal regions linked to muscle area and bone cross-sectional, knee flexors, and extensors isometric torque in twins. The authors concluded that many genes still have little explanation for muscle strength determination (De Mars et al 2008). Liu et al (2009) studied the association of the thyrotrophinreleasing hormone receptor (TRHR) gene and fat-free mass (FFM) in 1,000 individuals.…”

Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene

“…Genetic linkage studies regarding muscle strength are even scarcer. To date, only Tiainen et al 8 and our research group [9][10][11][12][13][14] reported results on genetic linkage for skeletal muscle strength characteristics. We were the first to perform linkage analyses on a unique collection of young male Caucasian siblings drawn from the Leuven Genes for Muscular Strength study (LGfMS).…”