PMID- 28564610
OWN - NLM
STAT- MEDLINE
DCOM- 20180305
LR  - 20191008
IS  - 2211-1247 (Electronic)
VI  - 19
IP  - 9
DP  - 2017 May 30
TI  - Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and 
      Association with Pain Phenotypes.
PG  - 1940-1952
LID - S2211-1247(17)30643-5 [pii]
LID - 10.1016/j.celrep.2017.05.018 [doi]
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.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Parisien, Marc
AU  - Parisien M
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada.
FAU - Khoury, Samar
AU  - Khoury S
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada.
FAU - Chabot-Dore, Anne-Julie
AU  - Chabot-Dore AJ
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada.
FAU - Sotocinal, Susana G
AU  - Sotocinal SG
AD  - Department of Psychology, McGill University, Montreal, QC H3A 0G4, Canada.
FAU - Slade, Gary D
AU  - Slade GD
AD  - 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.
FAU - Smith, Shad B
AU  - Smith SB
AD  - Department of Anesthesiology, Center for Translational Pain Medicine, Duke 
      University, Durham, NC 27708, USA.
FAU - Fillingim, Roger B
AU  - Fillingim RB
AD  - Department of Community Dentistry and Behavioral Science, University of Florida, 
      Gainesville, FL 32611, USA.
FAU - Ohrbach, Richard
AU  - Ohrbach R
AD  - Department of Oral Diagnostic Services, University at Buffalo, Buffalo, NY 14228, 
      USA.
FAU - Greenspan, Joel D
AU  - Greenspan JD
AD  - Department of Neural and Pain Sciences, Brotman Facial Pain Clinic, University of 
      Maryland Dental School, Baltimore, MD 21201, USA.
FAU - Maixner, William
AU  - Maixner W
AD  - Department of Anesthesiology, Center for Translational Pain Medicine, Duke 
      University, Durham, NC 27708, USA.
FAU - Mogil, Jeffrey S
AU  - Mogil JS
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada; Department of Psychology, McGill University, Montreal, QC H3A 0G4, 
      Canada.
FAU - Belfer, Inna
AU  - Belfer I
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada. Electronic address: belferinna@gmail.com.
FAU - Diatchenko, Luda
AU  - Diatchenko L
AD  - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3A 
      0G4, Canada. Electronic address: luda.diatchenko@mcgill.ca.
LA  - eng
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - U01 DE017018/DE/NIDCR NIH HHS/United States
GR  - Z99 OD999999/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Ganglia, Spinal/*metabolism/*pathology
MH  - Gene Expression Regulation
MH  - Genetic Loci
MH  - *Genetic Variation
MH  - *Genome-Wide Association Study
MH  - Humans
MH  - Mice
MH  - Pain/*genetics
MH  - Phenotype
MH  - Quantitative Trait Loci/genetics
MH  - Transcriptome/genetics
PMC - PMC5524461
MID - NIHMS877337
OTO - NOTNLM
OT  - DRG
OT  - GWAS
OT  - QST
OT  - SNPs
OT  - dorsal root ganglion
OT  - eQTLs
OT  - expression quantitative trait loci
OT  - genome-wide association study
OT  - pain
OT  - quantitative sensory testing
OT  - single nucleotide polymorphism
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2017/06/01 06:00
MHDA- 2018/03/06 06:00
PMCR- 2018/05/30
CRDT- 2017/06/01 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/02/14 00:00 [revised]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/03/06 06:00 [medline]
PHST- 2018/05/30 00:00 [pmc-release]
AID - S2211-1247(17)30643-5 [pii]
AID - 10.1016/j.celrep.2017.05.018 [doi]
PST - ppublish
SO  - Cell Rep. 2017 May 30;19(9):1940-1952. doi: 10.1016/j.celrep.2017.05.018.