Dataset Information

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

ABSTRACT:

Background

A sedentary lifestyle is often assumed to lead to increases in body weight and potentially obesity and related diseases but in fact little is known about the genetic association between physical activity and body weight. We tested for such an association between body weight and the distance, duration, and speed voluntarily run by 310 mice from the F2 generation produced from an intercross of two inbred lines that differed dramatically in their physical activity levels.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Leamy LJ

PROVIDER: S-EPMC2760520 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Leamy Larry J LJ Pomp Daniel D Lightfoot J Timothy JT

Genetics, selection, evolution : GSE 20090923

<h4>Background</h4>A sedentary lifestyle is often assumed to lead to increases in body weight and potentially obesity and related diseases but in fact little is known about the genetic association between physical activity and body weight. We tested for such an association between body weight and the distance, duration, and speed voluntarily run by 310 mice from the F2 generation produced from an intercross of two inbred lines that differed dramatically in their physical activity levels.<h4>Meth ...[more]

PMID: 19775457

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Project description:ObjectivesWhile bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity.DesignObservational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively.SettingMultinational study of 9306 participants.ParticipantsParticipants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme.Outcome measuresLongitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included.ResultsAdequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ(2)=16.8; p<0.0001), but not change in weight (χ(2)=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ(2)=5.9; p=0.02) but not previous step count (χ(2)=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ(2) for previous weight measurements 747.3; p<0.0001) and physical activity (χ(2) for previous step count 432.6; p<0.0001), these effects were of limited clinical importance.ConclusionsWhile a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables.Trial registration numberNCT00097786.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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