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 D. Greenspan; William Maixner; Jeffrey S. Mogil; Inna Belfer; Luda Diatchenko

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English (US)
Pages (from-to)	1940-1952
Number of pages	13
Journal	Cell Reports
Volume	19
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2017.05.018
State	Published - May 30 2017

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2017.05.018

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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

Parisien, M, Khoury, S, Chabot-Doré, AJ, Sotocinal, SG, Slade, GD, Smith, SB, Fillingim, RB, Ohrbach, R, Greenspan, JD, Maixner, W, Mogil, JS, Belfer, I & Diatchenko, L 2017, 'Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes', Cell Reports, vol. 19, no. 9, pp. 1940-1952. https://doi.org/10.1016/j.celrep.2017.05.018

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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.",

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AU - Khoury, Samar

AU - Chabot-Doré, Anne Julie

AU - Sotocinal, Susana G.

AU - Slade, Gary D.

AU - Smith, Shad B.

AU - Fillingim, Roger B.

AU - Ohrbach, Richard

AU - Greenspan, Joel D.

AU - Maixner, William

AU - Mogil, Jeffrey S.

AU - Belfer, Inna

AU - Diatchenko, Luda

PY - 2017/5/30

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N2 - 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.

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

Abstract

Keywords

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