The model that best fit the data was one in which risk alleles were sampled proportional to their occurrence in 1000 Genomes data, with a goodness-of-fit adjusted R2 = 0.49. Notably, the largest proportion of expected heritability was not explained by SNPs in the higher frequency allele bins (0.3–0.4 and 0.4–0.5), contrary to what was observed in Davis et al. (5). In addition, we observed that SNPs with low MAF (0.01–0.05) are expected to account for 10.4% of the heritability under this model, similar to the 10% that we observed and in contrast to Davis where low MAF SNPs accounted for almost no heritability. These discrepancies and the smaller ones observed in our study track with sample size. For example, the sample size for Davis et al. (1061 cases and 4236 controls) was smaller than our current study and variance of estimates are a direct function of sample size. Combining results from both studies demonstrated strong concordance with expectation (Figure 1C). In addition, prior studies (5,16) are likely more ancestrally heterogeneous than our present Swedish sample which can lead to increased variance.
