INSIG2 and obesity due to melanocortin 4 receptor deficiency: In addition to the above cases that were taken directly from rSNP_Guide database, from two recent publications we examined the non-coding SNPs (three in total) within or around two genes, namely INSIG2 [65] and TCF7L2 [66], that represent extremely rare examples of variants associated with complex disease (obesity and diabetes respectively in this case) that have been validated across diverse and multiple human cohorts.