Gene-environment (GE) interactions involving the IGF pathway may affect childhood obesity. Detecting such interactions using longitudinal family studies requires accounting for individual and familial correlations. Simulations were performed to study three methods to test for GE interactions in longitudinal family data using repeated outcomes (linear mixed model) or individual outcome averages as summary statistics (twin model, partition based score I test). Interactions between the IGF pathway genes (IGF-1, IGFALS) and environmental factors (physical activity, daycare attendance and sleep duration) were tested using the Quebec Newborn Twin Study data. The twin model yielded the best performance. Results from the QNTS analysis showed suggestive association for an IGF-1 variant at position 102791894 of chromosome 12 interacting with physical activity. However, this association was not statistically significant after multiple testing correction. More robust methods and studies are needed to better understand the IGF pathway’s role in childhood obesity.