For the gene-level metric, the excess in the number of OMIM genes that are proximate to a GWS SNP (compared with matched sets of random genes) plateaus at sample sizes of larger than 1.5 million, whereas the relative enrichment of GWS SNPs near OMIM genes first decreases with sample size, then plateaus when n is greater than 1.5 million (Supplementary Fig. 23a–c). Notably, the decrease observed for n values of less than 1.5 million reflects the preferential localization of larger effect variants (those identified with smaller sample sizes) closer to OMIM genes (Supplementary Fig. 23d) and, conversely, that more recently identified variants with smaller effects tend to localize further away from OMIM genes (Supplementary Fig. 23e). We also investigated the number of genes prioritized using SMR (hereafter referred to as SMR genes; Methods) using expression quantitative trait loci (eQTLs) as genetic instruments (Supplementary Table 16) as an alternative gene-level metric and found it to saturate for n values greater than 4 million (Supplementary Fig. 23f). Note that saturation of SMR genes is partly affected by the statistical power of current
