Don't throw the baby out with the bathwater: enabling a bottom-up approach in genome-wide association studies.

The current model for conducting genome-wide association studies (GWAS) is primarily phenotype-driven. In this “top-down” approach, the model is the case-control study, where participants are enrolled based on the presence or absence of a clinical phenotype, for example, cardiovascular disease or breast cancer (Pennisi 2007; Wellcome Trust Case Control Consortium 2007). The International HapMap Project has identified a large number of single nucleotide polymorphisms (SNPs) in the human population that enable investigators to genotype subjects for these various polymorphisms and determine associations with a phenotype of interest (Fig. 1A) (International HapMap Consortium et al. 2007).