Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3

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.

Genes and the ageing muscle: a review on genetic association studies

“…This would imply that different muscle phenotypes share the same chromosomal region with suggestive or significant evidence for linkage (De Mars et al 2008). …”

How pleiotropic genetics of the musculoskeletal system can inform genomics and phenomics of aging

“…Muscle mass and crosssectional area are highly heritable, ranging from 60% to 90% (Huygens et al 2004;Seeman et al 1996;Hsu et al 2005). Muscle strength is also influenced by genetic factors, with h 2 estimates ranging from 30% to 65% (De Mars et al 2008). …”

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).…”