In theory, GWA studies could at some point reach saturation for discovering new loci. It is becoming clear that many associated loci have multiple causal common variants, so at some point new variants could fall largely or exclusively in already-identified loci. This outcome is similar to a saturation mutagenesis scan in model organisms, where discovery of multiple alleles at each locus suggests that few new loci will be discovered by analyzing more mutants. If the main goal of GWA studies is to identify new loci and hence new biology (30) , then a diminishing return in new loci would strongly suggest that little would be gained by continuing. However, if the goal is to account for as yet unexplained heritability (67) then larger studies may yield more information, even if few new loci emerge. In either case, a key consideration is whether the new information – either new loci or increased variance explained – will be helpful in understanding the underlying biology and in treating or preventing disease. Often, these considerations will depend in an idiosyncratic fashion on the particular clinical features of the disease and on available treatments and preventive measures.
