Exploring regulation in tissues with eQTL networks

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 bet...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 114; no. 37; pp. E7841 - E7850
Main Authors Fagny, Maud, Paulson, Joseph N., Kuijjer, Marieke L., Sonawane, Abhijeet R., Chen, Cho-Yi, Lopes-Ramos, Camila M., Glass, Kimberly, Quackenbush, John, Platig, John
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 12.09.2017
SeriesPNAS Plus
Subjects
Biological activity
Biological Sciences
Chromatin
Coalescing
Communities
Gene expression
Genotype & phenotype
Life Sciences
Networks
PNAS Plus
Quantitative trait loci
Structure-function relationships
Studies
Tissues
GTEx
expression quantitative trait locus
GWAS
eQTL
bipartite networks
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Summary: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.
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PMCID: PMC5604022
Author contributions: M.F., J.N.P., M.L.K., A.R.S., C.-Y.C., C.M.L.-R., K.G., J.Q., and J.P. designed research; M.F. and J.P. performed research; M.F., J.N.P., J.Q., and J.P. analyzed data; and M.F., J.N.P., M.L.K., A.R.S., C.-Y.C., C.M.L.-R., K.G., J.Q., and J.P. wrote the paper.
Edited by Jasper Rine, University of California, Berkeley, CA, and approved August 4, 2017 (received for review May 3, 2017)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1707375114