During the past two decades, a great number of studies have been published purporting to have identified gene variants that predispose to obesity [as summarized in (9)].The credibility and relevance of these studies is indicated by the success of replication attempts within and beyond the geographic and ethnic groups from which the original reports hailed. Unfortunately, very few of these earlier reports have been adequately replicated. Thus, the identification of the FTO locus in 2007 (3) and the subsequent discovery of several other genetic risk factors for obesity (4–7) marked an important breakthrough in comprehending the genetic basis of common obesity. However, the extension of the initial studies' findings to more detailed and complex disease phenotypes is necessary if the clinical relevance of genetic variation is to be ascertained. Figure 1 illustrates the total difference in body mass between major and minor allele homozygotes at each of the obesity-associated loci, with the weight difference attributable to total, abdominal and gynoid adipose tissue overlaid. While these data illustrate that the weight differences observed for all of the variants are largely related
