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Cell Rep. 2017 May 30;19(9):1940-1952. doi: 10.1016/j.celrep.2017.05.018.

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

Author information

1
Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 0G4, Canada.
2
Department of Psychology, McGill University, Montréal, QC H3A 0G4, Canada.
3
Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
4
Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC 27708, USA.
5
Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL 32611, USA.
6
Department of Oral Diagnostic Services, University at Buffalo, Buffalo, NY 14228, USA.
7
Department of Neural and Pain Sciences, Brotman Facial Pain Clinic, University of Maryland Dental School, Baltimore, MD 21201, USA.
8
Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 0G4, Canada; Department of Psychology, McGill University, Montréal, QC H3A 0G4, Canada.
9
Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 0G4, Canada. Electronic address: belferinna@gmail.com.
10
Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 0G4, Canada. Electronic address: luda.diatchenko@mcgill.ca.

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.

KEYWORDS:

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

PMID:
28564610
PMCID:
PMC5524461
DOI:
10.1016/j.celrep.2017.05.018
[Indexed for MEDLINE]
Free PMC Article

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