Abstract
Purpose :
There is evidence suggesting an underlying genetic contribution in chronic pain conditions, as well as the co-existence of these conditions with neuropathic ocular pain (NOP). Therefore, it is possible that there are genomic variants that may predispose an individual for NOP development. We conducted a genome wide association study (GWAS) on individuals with NOP symptoms to identify genomic patterns.
Methods :
A total of 329 patients from the Miami Veterans Affairs (VA) eye clinic were recruited. The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-E; range 0-100) was completed for each patient to calculate a NPSI-E-sub-score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-E-sub-score with a significance threshold of p<5x10-8. A gene-based analyses was performed using the multi-marker analysis of genomic annotation (MAGMA) software (in the Functional Mapping and Annotation (FUMA) online platform). Input SNPs from our GWAS analysis were mapped to 10834 protein coding genes, and significant genes were run through gene set enrichment analysis (GSEA).
Results :
171 single nucleotide polymorphisms (SNPs) reached a threshold of p<10-5, of which 10 SNPs reached the suggestive level of significance of p<5x10-7 and 1 SNP met our genome wide significance threshold. This SNP (P=1.23x10-8) is located on chromosome 11q within an intron of a recently discovered lncRNA. Gene-based analyses demonstrate association with five genes. From GSEA, the top hits were associated with neuronal processes including synapse (false discovery rate (FDR)=6.93x10-17), neurogenesis (FDR=1.97x10-14), neuron development (FDR=2.37x10-14), and neuron differentiation (FDR=3.98x10-13).
Conclusions :
Our GWAS and gene-based association tests revealed genes with protein products that may impact morphogenesis and neuronal processes, lending biological plausibility to a potential impact of the enriched SNPs from our GWAS on NOP development. By identifying genetic polymorphisms related to NOP, potential therapeutic targets can be identified for novel treatments.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.