Exploring regulation in tissues with eQTL networks

Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7841-E7850. doi: 10.1073/pnas.1707375114. Epub 2017 Aug 29.

Abstract

Characterizing the collective regulatory impact of genetic variants on complex phenotypes is a major challenge in developing a genotype to phenotype map. Using expression quantitative trait locus (eQTL) analyses, we constructed bipartite networks in which edges represent significant associations between genetic variants and gene expression levels and found that the network structure informs regulatory function. We show, in 13 tissues, that these eQTL networks are organized into dense, highly modular communities grouping genes often involved in coherent biological processes. We find communities representing shared processes across tissues, as well as communities associated with tissue-specific processes that coalesce around variants in tissue-specific active chromatin regions. Node centrality is also highly informative, with the global and community hubs differing in regulatory potential and likelihood of being disease associated.

Keywords: GTEx; GWAS; bipartite networks; eQTL; expression quantitative trait locus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression / genetics
  • Gene Expression Regulation / genetics
  • Gene Regulatory Networks / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Organ Specificity / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics*
  • Quantitative Trait Loci / physiology
  • Transcriptome / genetics