One explanation for the failure of GWAS applied to MD might be that the causative variants, or markers sufficiently close to them, have not been genotyped on the available arrays. In fact, due to the blocks of linkage disequilibrium, in non-African populations GWAS is remarkably effective at detecting a large fraction of common variants of reasonable effect size (odds ratios greater than 1.2) that contribute to complex traits, even though a very small fraction of the total amount of sequence variation segregating in a population is actually genotyped. To illustrate this, Figure 1 shows the results of simulations that compare GWAS carried out using an Affymetrix 500K genotyping array, with the results from using all the variants in HapMap (Frazer et al., 2007). Even this relatively sparse array (current platforms interrogate millions of variants) has power of 82% (for a sample size of 9,000) to detect a locus with an odds ratio of ≥1.2, compared to 88% with the complete set of SNPs (9,240 is the largest discovery sample size used in GWAS of MD [Ripke et al., 2013b]). In
