LEP and obesity due to melanocortin 4 receptor deficiency: The heritability of BMI has been estimated as 30–40% based on a recent study.141 Furthermore, some investigations found that loss of function in genetic levels for leptin, leptin receptor, melanocortin 4 receptor, and others might cause severe obesity in humans.142,143 Therefore, obesity most likely results from a concerted interplay of genetic and environmental factors.