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

Publication date: 30 May 2017
Source:Cell Reports, Volume 19, Issue 9
Author(s): Marc Parisien, Samar Khoury, Anne-Julie Chabot-Doré, Susana G. Sotocinal, Gary D. Slade, Shad B. Smith, Roger B. Fillingim, Richard Ohrbach, Joel D. Greenspan, William Maixner, Jeffrey S. Mogil, Inna Belfer, Luda Diatchenko
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.

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Teaser

Parisien et al. present a database of expression quantitative trait loci in human dorsal root ganglia. The dataset represents a tool for interpreting human GWAS with sensory components. Its analysis demonstrates contributions of the HLA locus to pain phenotypes.


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