Replication has proven to be an essential component to any genetic association study [Chanock, et al. 2007]. A contributing factor to the success of GWAS was the standardized requirement for independent replication [Chanock, et al. 2007; Kraft, et al. 2009]. The division of GWAS studies into discovery and replication was also motivated by GWAS being expensive, and follow-up genotyping more cost efficient. As we combine and create studies large enough to reach adequate power in the discovery phase, it may not be possible to have large studies for replication [Hernan and Savitz 2013]. Current practice often focuses on whether stringent genome-wide significance standards are achieved for combined analysis of all available data [Eeles, et al. 2013; Michailidou, et al. 2013; Skol, et al. 2006]
