Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases

• Main Authors: Marbach, Daniel (Author), Lamparter, David (Author), Quon, Gerald (Contributor), Kellis, Manolis (Contributor), Kutalik, Zoltán (Author), Bergmann, Sven (Author)
• Other Authors: Broad Institute of MIT and Harvard (Contributor), Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2017-08-31T17:40:05Z.
• Subjects: Article
• Online Access: Get fulltext

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