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.
A replication study of pain interactions with comorbidities
Expression quantitative trait loci (eQTL) are single nucleotide polymorphisms (SNP) for which expression level of a given gene is found to be strongly associated with allele content at the SNP. Dorsal root ganglia (DRG) relay sensory information from periphery into the central nervous system, therefore can be seen as sensory gates modulating intensity of pain. In the OPPERA cohort (dbGaP phs000762), we find that SNPs in the HLA MHC class II locus are strongly associated with facial and back pains GWAS, which signal also coincide with eQTL in DRG. We used data from UKBB cohort to replicate the finding of the OPPERA cohort, more specifically GWAS of chronic (3+ months) facial and back pains. SNPs identified in the OPPERA cohort are significantly enriched for stronger association in the UKBB cohort, for both facial and back pains, therefore replicating OPPERA's original findings.
|Lead investigator:||Professor Luda Diatchenko|
|Lead institution:||McGill University|
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