Progress in the genetics of common obesity: size matters

Abstract

Over the past two decades serious efforts has been invested in the search for genes that predispose to common obesity, but progress has been slow and success limited. Genome-wide association, however, has revived optimism. Here we review recent advances in the field of obesity genetics and discuss the most important findings of candidate gene, genome-wide linkage studies and genome-wide association studies. We conclude by speculating about the way forward in the near future. Although large-scale candidate gene studies have placed MC4R more firmly on the human obesity map, the major breakthrough in obesity genetics was the discovery of FTO through genome-wide association. Variants located in the first intron of FTO were unequivocally associated with a 1.67-fold increased risk for obesity and a 0.40-0.66 kg/m2 increase in body mass index. Genome-wide association promises to enhance greatly our understanding of the genetic basis of common obesity, although candidate gene studies will remain a valuable approach because they allow more detailed analyses of biologically relevant candidates. A key factor contributing to continued success lies in large-scale data integration through international collaboration, which will provide the sample sizes required to identify genetic association with conclusive evidence.