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

Nat Methods. 2016 Apr;13(4):366-70. doi: 10.1038/nmeth.3799. Epub 2016 Mar 7.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases / genetics*
  • Brain Diseases / metabolism*
  • Cell Lineage / genetics*
  • Computational Biology / methods*
  • Epigenomics*
  • Gene Regulatory Networks*
  • Genetic Variation / genetics
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Organ Specificity
  • Promoter Regions, Genetic / genetics
  • Protein Interaction Mapping / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Transcription Factors