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

Marc Parisien | Zendy; Samar Khoury | Zendy; AnneJulie ChabotDoré | Zendy; Susana G. Sotocinal | Zendy; Gary D. Slade | Zendy; Shad B. Smith | Zendy; Roger B. Fillingim | Zendy; Richard Ohrbach | Zendy; Joel D. Greenspan | Zendy; William Maixner | Zendy; Jeffrey S. Mogil | Zendy; Inna Belfer | Zendy; Luda Diatchenko | Zendy

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

Author(s) -

Marc Parisien,

Samar Khoury,

AnneJulie ChabotDoré,

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

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.05.018

Subject(s) - phenotype , gene , dorsum , biology , genetics , gene expression , association (psychology) , neuroscience , anatomy , psychology , psychotherapist

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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