John Stamatoyannopoulos and colleagues report the enrichment of common disease-associated SNPs in regulatory DNA (Science, published online 5 September 2012; doi:10.1126/science.1222794). They performed genome-wide DNase I mapping in 349 cell and tissue samples from the ENCODE Project and the Roadmap Epigenomics Program. An average of 198,180 DNase I hypersensitive sites (DHSs) were identified per cell type, with 3,899,693 distinct DHS positions identified in total. The authors compared these sites to noncoding GWAS-identified SNPs associated with 207 diseases and 447 quantitative traits, finding enrichment of these SNPs in DHSs, with 57.1% of all noncoding GWAS SNPs found within a DHS and a further 19.5% in complete linkage disequilibrium. This enrichment increased with both the strength and the extent of replication of the SNP-trait association. The authors also generated DNS maps from 233 fetal tissue samples and found that 88.1% of the noncoding SNPs were located within DHSs that are active in fetal cells, with 30.3% showing fetal stage–specific DHS activity that was not found in adult cells. The genic targets of 419 DHSs harboring disease-associated SNPs were identified, with many acting over a distance. The authors found that SNPs clustered in transcriptional regulatory pathways relevant to the disorder with which they were associated, with related diseases also showing a shared network.