Replication studies should have sufficient sample size to detect the effect of the susceptibility allele. Often, the effects identified in an initial GWAS suffer from winner's curse, where the detected effect is likely stronger in the GWAS sample than in the general population [44]. This means that replication samples should ideally be larger to account for the over-estimation of effect size. With replication, it is important for the study to be well-powered to identify spuriously associated SNPs where the null hypothesis is most likely true – in other words, to confidently call the initial GWAS result a false-positive.
