To investigate these differences, we estimated what the expected portion of total heritability in these bins should be. First, we observed that the percentages of the total SNPs in each bin were distributed differently in comparison to 1000 Genomes data (for SNPs with MAF > 0.01) (Tables S6 and S7), which we would expect is more representative of variation in the general population. For example, 45.2% of the SNPs in our study had MAF between 0.01 and 0.05, while 29.5% of SNPs in 1000 Genomes data had MAF between 0.01 and 0.05. Under the standard quantitative genetic “infinitesimal model” (also referred to as the “polygenic model”) (31), it is reasonable to assume the effect of all risk SNPs is equal. With this assumption, we then explored various models to predict the expected heritability in each MAF bin (Figure 1; Tables S6–S8; Figures S10 and S11).
