An estimated 40 to 70% of the variation in obesity susceptibility observed in the population is due to inter-individual genetic differences.1,2 Despite this substantial genetic contribution, the identification of genes associated with obesity traits was, for many years, hampered by a limited understanding of the genetic architecture of the human genome and the biological pathways implicated in obesity.3 However, the advent of the genome-wide association approach in 2005, a hypothesis-free approach made possible through advances in high throughput genotyping technology, has dramatically increased the pace of gene discovery. To date, genome-wide association studies (GWAS) have identified approximately 2,000 genetic loci with robust associations for more than 300 common traits and diseases,4,5 including at least 75 obesity-susceptibility loci.6,7 FTO (fat mass and obesity associated gene) was the first obesity-susceptibility gene identified through GWAS,8,9 and continues to be the locus with the largest effect on body mass index (BMI) and obesity risk, most widely replicated with variety of obesity traits throughout the life course and across diverse ancestries.7 Here, we review the discovery of FTO as an obesity gene and the insights
