While there has been a very public focus on the failure of GWAS to find the missing heritability5,6, the simplest explanation for this is that the expectations were based on unrealistic prior assumption of effect sizes. Once it is accepted that most alleles are associated with relative risks less than 1.2, it becomes clear that hundreds of thousands of individuals are required to identify more than a few dozen loci than explain more than 20% of the variance. In fact, sample sizes can be extrapolated from the range of variant effects in initial discovery samples12, and in the case of height, the GIANT consortium (http://www.broadinstitute.org/collaboration/giant/) confirmed the inferences from 30,000 individuals100 when they jumped to 180,000, finding an additional 180 or so loci14. Simply put, the data is generally consistent with the infinitesimal model to a first approximation, even where variants are yet to be identified. It is the common variant of moderate effect version of the CD-CV model that needs to be discarded.
