Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease

Genome Med. 2018 Jun 27;10(1):48. doi: 10.1186/s13073-018-0558-x.


Background: The genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel disease and juvenile idiopathic arthritis are both clinically heterogeneous and known to be due in part to abnormal regulation of gene activity in diverse immune cell types. Comparative genomic analysis of these conditions is expected to reveal differences in underlying genetic mechanisms of disease.

Methods: We performed RNA-Seq on whole blood samples from 202 patients with oligoarticular, polyarticular, or systemic juvenile idiopathic arthritis, or with Crohn's disease or ulcerative colitis, as well as healthy controls, to characterize differences in gene expression. Gene ontology analysis combined with Blood Transcript Module and Blood Informative Transcript analysis was used to infer immunological differences. Comparative expression quantitative trait locus (eQTL) analysis was used to quantify disease-specific regulation of transcript abundance.

Results: A pattern of differentially expressed genes and pathways reveals a gradient of disease spanning from healthy controls to oligoarticular, polyarticular, and systemic juvenile idiopathic arthritis (JIA); Crohn's disease; and ulcerative colitis. Transcriptional risk scores also provide good discrimination of controls, JIA, and IBD. Most eQTL are found to have similar effects across disease sub-types, but we also identify disease-specific eQTL at loci associated with disease by GWAS.

Conclusion: JIA and IBD are characterized by divergent peripheral blood transcriptomes, the genetic regulation of which displays limited disease specificity, implying that disease-specific genetic influences are largely independent of, or downstream of, eQTL effects.

Keywords: Gene expression; Inflammatory bowel disease; Juvenile idiopathic arthritis; eQTL.

Publication types

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

MeSH terms

  • Adolescent
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Gene Expression Regulation*
  • Genetic Heterogeneity
  • Genome-Wide Association Study
  • Humans
  • Infant
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / genetics*
  • Quantitative Trait Loci / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Risk Factors
  • Transcription, Genetic
  • Young Adult


  • RNA, Messenger