A variety of the approaches we used in conducting these studies should be of general utility in enrichment studies. It is clear, for example, that the MAF spectrum of SNPs associated with complex human traits is quite different than that of SNPs on the products used to conduct GWAS, or in the overall HapMap. The much higher minor allele frequencies observed for SNPs reproducibly associated with complex traits than for SNPs on high throughput platforms is a natural consequence of the increased power to detect associations for SNPs with higher minor allele frequencies. It is clearly critical to condition on the MAF in enrichment studies in which simulations are conducted using SNPs from high throughput platforms or from the HapMap, and to date, this has not been widely appreciated. The correlation among SNPs due to LD is a further complicating factor in conducting enrichment studies. We are confident that failure to adequately account for LD will not affect our estimate of the proportion of SNPs that are eQTLs, but rather the variance of this estimate. There are, however, more subtle
