Bone Quality, Muscle Mass, and Activity: Relationships and Genetic Influence

Open Access
Lang, Teresa Caroldean
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
June 17, 2003
Committee Members:
  • Neil Sharkey, Committee Chair
  • Gerald Eugene Mc Clearn, Committee Member
  • George Patrick Vogler, Committee Member
  • Robert Barry Eckhardt, Committee Member
  • SEM
  • activity
  • muscle
  • genetics
  • bone
  • QTL
The primary aim of this study was to identify quantitative trait loci (QTL) for skeletal measures in C57BL/6J x DBA/2 F2 and RI populations of mice. QTL analysis is based on a genome-wide search for regions of chromosomes that contain a locus or gene that influences the phenotype. Multiple points along the genome are analyzed to determine the likelihood of a QTL at each position influencing the trait based on finding an association between the genotype of a genetic marker and the trait. Many skeletal studies have reported strong correlations between muscle, skeletal, and body size phenotypes and these correlations add to the difficulty in identifying direct genetic influence on skeletal traits. Quantitative trait loci (QTL) have been identified for skeletal phenotypes and it is often the case that QTLs for body size (body weight, body length, and lean body mass) phenotypes also map to these same areas. A QTL identified as influencing bone could act indirectly through body size or muscle mass. Identifying QTLs that influence skeletal phenotypes that are mediated through body size related pathways is informative, however it is also important to identify QTLs that influence skeletal phenotypes independent of body size. Removing size effects has been an issue for researchers and traditionally one method of removing the size effect has been through the use of ratios. This technique and an alternate technique of multiple regression were performed on muscle and skeletal data and the differences in results from these methods of normalization are discussed. The second aim of this study was to investigate the relationships between muscle mass, skeletal integrity, physical activity/behavior, and the influence of specific genetic loci that were identified for multiple traits in the same chromosomal region. Structural equation modeling (SEM) was used to investigate the direct and indirect relationships among activity, muscle and bone factors and five QTLs. This study has isolated and confirmed numerous QLTs influencing bone quality and provides evidence that many QTLs exert effects through complex pathways such as body size, muscle mass, and activity. This work fully illustrates the complex system responsible for the maintenance of skeletal integrity.