Genome-wide association studies (GWAS) have successfully identified polymorphisms that contribute to disease risk for numerous complex traits and diseases (Wellcome Trust Case Control Consortium 2007). GWAS for BMI and obesity using sample sizes in the tens of thousands have yielded many putative risk variants of individually small effect. The first common single nucleotide polymorphisms (SNPs) associated with BMI and common obesity were in the fat mass and obesity-associated (FTO) gene and near melanocortin 4 receptor (MC4R) and have been widely replicated (Frayling et al. 2007; Dina et al. 2007; Herbert et al. 2006; Scuteri et al. 2007; Hinney et al. 2007; Loos et al. 2008; Chambers et al. 2008). Additionally, two large-scale BMI metaanalyses, Thorleifsson et al. (2009) and Willer et al. (2009), yielded 13 genetic loci reaching genome-wide significance, including the previously implicated variants in or near FTO and MC4R. These variants were highly significant but had modest effects with 0.06–0.4 kg/m2 per allele change in BMI and modest obesity (BMI>30 kg/m2) odds ratios ranging 1.03–1.3. Although many loci are expected to contribute to a complex trait like BMI,
