Obesity and FTO: Changing Focus at a Complex Locus

The fat mass and obesity-associated (FTO) gene was placed center stage when common intronic variants within the gene were robustly associated with human obesity. Murine models of perturbed Fto expression have shown effects on body weight and composition. However, a clear understanding of the link between FTO intronic variants and FTO activity has remained elusive. Two recent reports now indicate that obesity-associated SNPs appear functionally connected not with FTO but with two neighboring genes: IRX3 and RPGRIP1L. Here, we review these new findings and consider the implications for future analysis of GWAS hits.