Genome-Wide Variant Associations and Biological Pathways in Postherpetic Neuralgia

Introduction: Postherpetic neuralgia (PHN) is the most frequent chronic complication of herpes zoster and is characterized by persistent neuropathic pain caused by sensory nerve injury and neuroinflammatory responses. Although clinical risk factors are well documented, the genetic architecture underlying PHN susceptibility remains poorly defined. Genome-wide association studies (GWASs) represent a powerful tool to identify common variants that may contribute to neuronal vulnerability, persistent inflammation, or dysregulated pain signaling.

Methods: We performed a secondary analysis of publicly available summary statistics from the GWAS Catalog (GCST012124), derived from a genome-wide association study conducted in individuals with PHN. The dataset included all reported SNP-level associations for the trait MONDO_0041052. Variants were evaluated based on reported effect allele, beta coefficients, p-values, genomic context, and nearest-gene annotation. Biological interpretation was performed through gene-function review and known pathways implicated in neuropathic pain.

Results: Five genome-wide significant or near-significant loci were identified. The strongest associations were rs4773840 mapped to KIF1B (β = 0.18, p = 3.8×10⁻⁸) and rs10982356 near PTPRZ1 (β = 0.17, p = 7.6×10⁻⁸), both genes involved in axonal transport, neuronal signaling, and glial modulation. Additional variants included rs9655009 within PRKCE (p = 4×10⁻⁷), a key kinase in nociceptive sensitization, rs10887816 near CXCR4, implicated in neuroinflammation, and rs17057519 in a regulatory non-coding region (WDR11-AS1). These loci converge on pathways relevant to neuronal injury, synaptic modulation, and chronic pain maintenance.

Conclusions: This GWAS highlights candidate genetic factors that may increase susceptibility to PHN by altering axonal integrity, inflammatory responses, and pain-signaling pathways. The findings support a multifactorial neurobiological basis for PHN and provide mechanistic targets for future translational and therapeutic research.