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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Parisien, M; Khoury, S; Chabot-Doré, A-J; Sotocinal, SG; Slade, GD; Smith, SB; Fillingim, RB; Ohrbach, R; Greenspan, JD; Maixner, W; Mogil, JS; Belfer, I; Diatchenko, L

Published Date

  • May 30, 2017

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 1940 - 1952

PubMed ID

  • 28564610

Pubmed Central ID

  • PMC5524461

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.05.018


  • eng

Conference Location

  • United States