even with missing variance, one of the benefits of GWAS is, in addition to predicting individual risk, their ability to expose biological pathways that underlie human disease (2,27). Given the extremely high resource-consuming nature of these follow-up studies, a clear and precise plan for the prioritization of variants is critical. Clearly those variants with the strongest statistical evidence of association will be pursued first, but as that evidence dwindles, some signals with no evidence of biological relevance may be traded for those meeting the biological priorities of the study when the difference in evidence for genotype–phenotype correlation is modest. As shown by Saccone et al. (4), this is what occurs when the GIN prioritization method is implemented after a GWAS: the difference between the set of SNPs selected by the GIN prioritization and straight P-value methods is roughly only one order of magnitude in association with P-value. The difference applies mainly to SNPs with moderate evidence for association—the potential ‘high hanging fruit’.
