In recent years, GWAS have greatly extended our knowledge of genetic loci associated with human disease risk and other phenotypes. The output of these studies is a series of SNPs (“GWAS SNPs”) correlated with a phenotype, although not necessarily the functional variants. Strikingly, 88% of associated SNPs are either intronic or intergenic75. We examined 4,860 SNP-phenotype associations for 4,492 SNPs curated in the NHGRI GWAS catalogue75. We found that 12% of these SNPs overlap TF-occupied regions whereas 34% overlap DHSs (Figure 10A). Both figures reflect significant enrichments relative to the overall proportions of 1000 Genomes project SNPs (about 6% and 23%, respectively). Even after accounting for biases introduced by selection of SNPs for the standard genotyping arrays, GWAS SNPs show consistently higher overlap with ENCODE annotations (Figure 10A, see Supplementary Information). Furthermore, after partitioning the genome by density of different classes of functional elements, GWAS SNPs were consistently enriched beyond all the genotyping SNPs in function-rich partitions, and depleted in function-poor partitions (see Supplementary Figure M1). GWAS SNPs are particularly enriched in the segmentation classes associated with enhancers and TSSs across several cell types (see Supplementary Figure M2).
