(A) We compared the performance of GoShifter with that of matching-based tests by using different parameters—(1) GEN, MAF, and TSS proximity and (2) GEN, LD, TSS proximity, and TES proximity—to match SNPs on. We generated sets of 1,416 SNPs tagging SNPs overlapping different genomic annotations; some SNP sets tagging SNPs in specific annotations (e.g., DHSs, promoter regions, 5′ UTRs, and nonsynonymous variants in exons) were enriched in DHSs, whereas others (e.g., 3′ UTRs, introns, and intergenic regions) were depleted in DHSs. For each functional model, we generated 1,000 sets of SNPs that we subsequently tested for enrichment in DHSs (left). The number of expected false positives at p < 0.05 is indicated by the dotted line. On the right, we plot the delta-overlap, which is the difference between the proportions of SNPs overlapping an annotation in the actual data and the proportion of SNPs overlapping an annotation in the null distribution.