MC4R and obesity due to melanocortin 4 receptor deficiency: Further, since gene-environment and gene-gene interactions may modulate the effect the variants exert on BMI, analyses are extended to investigate such interactions, focusing on physical activity as an environmental risk factor and on GWA identified obesity variants, reaching a stringent genome-wide significance threshold, (FTO rs9939609 and MC4R rs17782313) as genetic risk factors.