Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants

J Autoimmun. 2017 Jul:81:99-109. doi: 10.1016/j.jaut.2017.03.014. Epub 2017 Apr 15.


Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets.

MeSH terms

  • Adult
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy
  • Autoimmunity / genetics*
  • Biomarkers
  • Case-Control Studies
  • Computational Biology / methods
  • Disease Susceptibility
  • Enhancer Elements, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans
  • Middle Aged
  • Molecular Sequence Annotation
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • RNA, Long Noncoding / genetics*
  • Risk


  • Biomarkers
  • RNA, Long Noncoding