Genetic variation in the pleiotropic association between physical activity and body weight in mice

We used a conventional interval mapping approach with SNP markers to search for QTLs that affected both body weight and activity traits. We also conducted a genome scan to search for relationship QTLs (relQTLs), or chromosomal regions that affected an activity trait variably depending on the phenotypic value of body weight.We uncovered seven quantitative trait loci (QTLs) affecting body weight, but only one co-localized with another QTL previously found for activity traits. We discovered 19 relQTLs that provided evidence for a genetic (pleiotropic) association of physical activity and body weight. The three genotypes at each of these loci typically exhibited a combination of negative, zero, and positive regressions of the activity traits on body weight, the net effect of which was to produce overall independence of body weight from physical activity. We also demonstrated that the relQTLs produced these varying associations through differential epistatic interactions with a number of other epistatic QTLs throughout the genome.It was concluded that individuals with specific combinations of genotypes at the relQTLs and epiQTLs might account for some of the variation typically seen in plots of the association of physical activity with body weight.Mounting evidence suggests that physical activity is crucial for the health and well being of people of all ages, from very young children [1] to elderly adults [2]. Physical inactivity is well known to be associated with a diverse number of health problems such as coronary heart disease and colon cancer [3-6] and has been ranked as the second leading actual cause of death in the United States [7]. Sedentary lifestyles also are thought to promote obesity and associated diseases such as diabetes that have become a special concern in recent years because of their dramatic increase in frequency even in children [8]. Moreover, some studies have demonstrated beneficial effects of physical activity independent of body weight or weigh