Genome wide association (GWA) is a method of choice for identifying genes whose variants influence vulnerability to complex disorders. Declaring “replication” of individual results of genome wide association studies is straightforward when major gene effects provide associations between marker and phenotype that display the same phase and “genome wide” levels of significance (p ca 10−8) in each of several independent samples. However, such “template” replication for individual markers is unlikely to be achieved in many otherwise-reasonable samples for many phenotypes. Phenotypes and samples that display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity and sample-to-sample differences in fine structures of linkage disequilibrium can provide especial difficulties for this “template” approach. These difficulties can be exacerbated when data comes from different genotyping platforms that do not assess allele frequencies for identical sets of SNPs. Much current genome wide association and linkage data suggests that we may have identified many or even most of the loci at which we might expect “template” analyses to identify reproducible genome wide significance in reasonably sized samples (see references below). Much of the risk attributable to genetic
