Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes

Marc Parisien, Samar Khoury, Anne Julie Chabot-Doré, Susana G. Sotocinal, Gary D. Slade, Shad B. Smith, Roger B. Fillingim, Richard Ohrbach, Joel Daniel Greenspan, William Maixner, Jeffrey S. Mogil, Inna Belfer, Luda Diatchenko

Research output: Contribution to journalArticle

Abstract

Dorsal root ganglia (DRG) relay sensory information to the brain, giving rise to the perception of pain, disorders of which are prevalent and burdensome. Here, we mapped expression quantitative trait loci (eQTLs) in a collection of human DRGs. DRG eQTLs were enriched within untranslated regions of coding genes of low abundance, with some overlapping with other brain regions and blood cell cis-eQTLs. We confirm functionality of identified eQTLs through their significant enrichment within open chromatin and highly deleterious SNPs, particularly at the exon level, suggesting substantial contribution of eQTLs to alternative splicing regulation. We illustrate pain-related genetic association results explained by DRG eQTLs, with the strongest evidence for contribution of the human leukocyte antigen (HLA) locus, confirmed using a mouse inflammatory pain model. Finally, we show that DRG eQTLs are found among hits in numerous genome-wide association studies, suggesting that this dataset will help address pain components of non-pain disorders.

Original languageEnglish (US)
Pages (from-to)1940-1952
Number of pages13
JournalCell Reports
Volume19
Issue number9
DOIs
StatePublished - May 30 2017
Externally publishedYes

Keywords

  • dorsal root ganglion
  • DRG
  • eQTLs
  • expression quantitative trait loci
  • genome-wide association study
  • GWAS
  • pain
  • QST
  • quantitative sensory testing
  • single nucleotide polymorphism
  • SNPs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Parisien, M., Khoury, S., Chabot-Doré, A. J., Sotocinal, S. G., Slade, G. D., Smith, S. B., Fillingim, R. B., Ohrbach, R., Greenspan, J. D., Maixner, W., Mogil, J. S., Belfer, I., & Diatchenko, L. (2017). Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes. Cell Reports, 19(9), 1940-1952. https://doi.org/10.1016/j.celrep.2017.05.018