There are several possible extensions of the work presented here. First, SAGE participants consisted of a selected sample for substance-use behaviors. Although we have included AD and ND as covariates in all analyses, research has shown these phenotypes to have complex relationships with body composition [55, 56], and this may complicate interpretation. Future research should test for associations in both larger and population-based samples. An additional extension of this work is to incorporate variation detected from other obesity phenotypes such as waist-to-hip ratio [57, 58], extremes of the BMI trait distribution [59], and from diverse populations [14]. Additionally, fine mapping efforts are needed and will likely identify lower-frequency variants, which are typically not genotyped on commercial GWAS-arrays. Therefore a further extension of the work presented here is to include lower-frequency SNPs and INDELs identified by large-scale exome and genome sequencing efforts. Another important extension of an integrated model of BMI and obesity is to incorporate the moderating effects of the environment. At least two of the BMI-validated SNPs exhibit gene by environment interactions (GxE) [60, 61]. For example, a large
