Genetic determinants of BMI, diet, and fitness interact to partially explain anthropometric obesity traits but not the metabolic consequences of obesity in men and women
Authors' conclusion
The genetic factors influencing BMI appear to differ from those contributing to measures of adiposity and metabolic consequences of obesity. Genetic risk of high BMI was validated in this cohort, but sex, RMR, and fitness are the more refined determinants of adiposity and dysregulated metabolism in this healthy population. Future research should be sure to utilize genetic risk predictors specifically associated with maladaptive obesity traits rather than more broad associated phenotypes.
Study context
- Population
- Men and women aged 18–66 years from the USDA Nutritional Phenotyping Study
- Participants
- 211 men
- Outcome
- Variance of BMI, body composition and metabolic syndrome traits explained by BMI PRS
Methodological detailsage/sex/BMI-balanced sample
- age/sex/BMI-balanced sample
Main finding
As reported in the abstract
- BMI variance explained by polygenic risk scores (PRS) independently
- 15.6%
- BMI variance explained by PRS, adjusted for age, sex and genetic population structure (pANCOVA = 1.1 × 10⁻⁷)
- 11.3%
- Explained variance by PRS in best fit models: android-to-gynoid ratio
- 3.3%
- Explained variance by PRS in best fit models: lean mass index
- 6.6%
- Explained variance by PRS in best fit models: waist circumference
- 10.1%
Observational data: associations, not effects.
Original publication
Genetic determinants of BMI, diet, and fitness interact to partially explain anthropometric obesity traits but not the metabolic consequences of obesity in men and women. Int J Obes (Lond). Published 20 February 2026. doi:10.
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