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

• Type of Material: Article
• Authors: Angela Mo, Georgia Institute of Technology; Urko M. Marigorta, Georgia Institute of Technology; Dalia Arafat, Georgia Institute of Technology; Lai Hin Kimi Chan, Emory University; Lori Ponder, Emory University; Se Ryeong Jang, Emory University; Jarod Prince, Emory University; Subra Kugathasan, Emory University; Sampath Prahalad, Emory University; Greg Gibson, Georgia Institute of Technology
• Language: English
• Date: 2018-06-27
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13073-018-0558-x
• Title of Journal or Parent Work: Genome Medicine
• ISSN: 1756-994X
• Volume: 10
• Issue: 1
• Start Page: 48
• End Page: 48
• Grant/Funding Information: This research was funded by US NIH grants 1-P01-GM099568 (Project 3) to GG and 2-R01-DK087694 to SK and GG.; AM is supported by T32-GM105490. SP is supported by Marcus Foundation Inc. Atlanta, GA.
• Keywords: Life Sciences & Biomedicine; ASSOCIATION; SUSCEPTIBILITY LOCI; EQTLS; IMMUNE-SYSTEM; RISK; CLASSIFICATION; Inflammatory bowel disease; Gene expression; AUTOIMMUNE-DISEASES; QUANTITATIVE TRAIT LOCI; Science & Technology; Genetics & Heredity; PATHOGENESIS; PROFILES; Juvenile idiopathic arthritis; eQTL
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

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.