From GWAS to biology: lessons from FTO

Genome-wide association studies have been very powerful, uncovering potentially new biology that would not have been possible using a candidate gene approach. A prime example of this is the gene FTO (fat mass and obesity associated), which first came to light in 2007, when single nucleotide polymorphisms in its first intron were robustly associated with body mass index and obesity. Subsequently, as it became clear that this association with body weight, and increasingly food intake, was replicable across multiple populations and different age groups, attention was turned to studying the biology of FTO, about which absolutely nothing was known. This review focuses on the genetic and biochemical approaches as well as animal models that have been used by us and others since 2007 to try and uncover the complex biology of FTO.