• Adolescence;
  • BMI;
  • genetics;
  • race/ethnicity


What is already known about this subject

  • Genome-Wide Association Studies have successfully identified numerous genetic loci that influence body mass index in European-descent middle-aged adults.
  • Adolescence is a high-risk period for the development of adult obesity and severe obesity.
  • Physical activity is one of the most promising behavioural candidates for preventing and reducing weight gain, particularly among youth.

What this study adds

  • An examination of the joint association between 41 of the well-established obesity susceptibility single-nucleotide polymorphisms with <5 vs. ≥5 bouts of moderate to vigorous physical activity (MVPA) per week in relation to body mass index (BMI)-for-age Z-score in a nationally representative sample of European American, African–American and Hispanic American adolescents.
  • Three nominally significant interactions (P < 0.05) varied by race/ethnicity.
  • Overall, the estimated effect of the risk allele on BMI-for-age Z-score was greater in individuals with <5 than those with ≥5 bouts MVPA per week.


Little is known about the interaction between genetic and behavioural factors during lifecycle risk periods for obesity and how associations vary across race/ethnicity.


The objective of this study was to examine joint associations of adiposity-related single-nucleotide polymorphisms (SNPs) and moderate to vigorous physical activity (MVPA) with body mass index (BMI) in a diverse adolescent cohort.


Using data from the National Longitudinal Study of Adolescent Health (n = 8113: Wave II 1996; ages 12–21, Wave III; ages 18–27), we assessed interactions of 41 well-established SNPs and MVPA with BMI-for-age Z-scores in European Americans (EA; n = 5077), African–Americans (AA; n = 1736) and Hispanic Americans (HA; n = 1300).


Of 97 assessed, we found nominally significant SNP–MVPA interactions on BMI-for-age Z-score in EA at GNPDA2 and FTO and in HA at LZTR2/SEC16B. In EA, the estimated effect of the FTO risk allele on BMI-for-age Z-score was lower (β = −0.13; 95% confidence interval [CI]: 0.08, 0.18) in individuals with ≥5 vs. <5 (β = 0.24; CI: 0.16, 0.32) bouts of MVPA per week (P for interaction 0.02). Race/ethnicity-pooled meta-analysis showed nominally significant interactions for SNPs at TFAP2B, POC5 and LYPLAL1.


High MVPA may attenuate underlying genetic risk for obesity during adolescence, a high-risk period for adult obesity.