Genome-wide association study of neuropathic pain

Neuropathic pain is a complex chronic condition with a multifactorial etiology that includes genetic susceptibility. However, the genetic basis of neuropathic pain remains poorly understood. We aimed to investigate genetic variants associated with the presence and intensity of neuropathic pain using genome-wide association analyses in the GeNeuP cohort, comprised of 1146 deeply phenotyped individuals with peripheral neuropathy from Norway. Genotyping was performed using the Illumina Global Screening Array, and analyses were conducted to test associations with the presence and intensity of neuropathic pain. No significant associations were detected at the genome-wide significance level ( P < 5 × 10 -8 ) for either the presence or intensity of neuropathic pain. However, at the subthreshold level ( P < 10 -6 ), 3 single nucleotide polymorphisms (annotated to the CHRDL1 and MCF2L gene and a long non-coding RNA) were associated with intensity of neuropathic pain. A targeted candidate gene analysis of 163 genes previously implicated in neuropathic pain and neuropathy did not yield significant associations. These results highlight the complexity of the genetic architecture underlying neuropathic pain and the challenges in identifying common variants with detectable effects. The identification of subthreshold associations of genes involved in synaptic plasticity is intriguing and merits further investigation. Larger studies with refined phenotyping will be essential to validate these signals and to advance understanding of the genetic contributors to neuropathic pain.