Results of genome-wide association studies (GWAS) in complex traits published to date have provided us with surprisingly little new information on the nature of the genetic component to these phenotypes, despite the large number of single nucleotide polymorphisms (SNPs) found to be reproducibly associated with such traits. In some cases, this reflects the fact that major aspects of the biological basis for disease were already well understood; results of GWAS in autoimmune disorders, for example, have reinforced the central importance of the immune system and its regulation. For a few disorders, results of GWAS have highlighted biological contributing factors to disease that had not previously been recognized as central, such as the complement system in macular degeneration [1] or autophagy in Crohn's disease [2]–[4]. While it does seem ungrateful to question the utility of GWAS when they have yielded so many more reproducible associations than we have achieved with any other approach, the fact is that our primary goal in conducting GWAS for a complex trait – achieving a comprehensive understanding of the genetic basis for that trait – remains
