The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.

ABSTRACT: Chronic pain is a complex clinical problem comprising multiple conditions that may share a common genetic profile. GWAS have identified many risk loci whose cell-type context remains unclear. Here, we integrated GWAS data on chronic pain with single-cell RNA-Seq (scRNA-Seq) data from human brain and dorsal root ganglia (hDRG) and single-cell chromatin accessibility data from human brain and mouse dorsal horn. Pain-associated variants were enriched in glutamatergic neurons, mainly in the prefrontal cortex, hippocampal CA1-3, and amygdala. In hDRG, the hPEP.TRPV1/A1.2 neuronal subtype showed robust enrichment. Chromatin accessibility analyses revealed variant enrichment in excitatory and inhibitory neocortical neurons in the brain and in midventral neurons and oligodendrocyte precursor cells

SUBMITTER: Toikumo S 

PROVIDER: S-EPMC12700546 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature