In this article we review the requirements for replicating associations discovered via GWA studies in light of recent developments: in particular, the increasing role of consortia of multiple GWA studies. Prospective meta-analysis of multiple genome-wide studies (conducted by different investigative teams, in different populations, using different technologies and different designs) can satisfy the requirement for replication in the context of gene discovery, without the need to genotype yet more samples in yet further studies, as long as the combined evidence for association is strong and consistent.[7] This is an important point, since very large samples sizes are required to reliably identify common variants with modest effects, and formal replication of an association—i.e. genotyping the initially discovered genetic variant in a new, completely independent sample of sufficient size—may be too expensive in terms of time, money, and available samples. Indeed, for some rare diseases (e.g. Creutzfeldt Jakob disease) or relatively uncommon diseases (e.g., pancreatic cancer), most if not all samples with readily-available DNA may be genotyped as part of initial GWA studies used at the discovery stage.
