INSIG2 and obesity due to melanocortin 4 receptor deficiency: The later study showed a stronger INSIG2-obesity-association compared to the earlier study: This raised the additional question whether the changes in nutritional intake and physical activity [14],[15] believed to contribute to the increase in the prevalence of obesity during the last decades were the reason for some of the between-study heterogeneity observed for this SNP's association with obesity.