GWAS SNP arrays necessarily include SNPs with a wide distribution of minor allele frequencies (MAFs), from nearly monomorphic (MAF <0.5%) to very common (MAF≈50%). All of the methods for determining SNP selection implicitly assume that the p-values or test statistics from individual SNPs are drawn from the same distribution, regardless of MAF. If this were true, then ranking the test statistics from SNPs of different MAF would be valid. However, the power to detect a given genetic effect with a given study size depends to a great extent on the MAF of the risk allele tested. Specifically, loci with a low MAF (<10%) have significantly lower power to detect weak genotypic risk ratios than loci with a high MAF (>40%) [1]. Further, previous studies have demonstrated that rare genotypes are more likely to result in spurious findings [2]. Thus, many GWAS have removed SNPs with MAF<10% [3,4].
