Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants--including variants that do not reach genome-wide significance--often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org). hs_blood_network.rds : human blood related gene regulatory networks (R program data file) hs_pantissue_network.rds : human pan-tissue related gene regulatory networks (R program data file) mm_blood_network.rds : mouse blood related gene regulatory networks (R program data file) mm_pantissue_network.rds : mouse pan-tissue related gene regulatory networks (R program data file) PMID: 26950747 PMCID: PMC4967716 DOI: 10.1038/nmeth.3799