Genome Wide Association Study of Neuropathic Ocular Pain

Abstract

Purpose: To conduct a genome-wide association study (GWAS) of individuals with neuropathic ocular pain (NOP) symptoms to identify genomic variants that may predispose to NOP development. Design: Prospective study of individuals with NOP. Participants: Three hundred twenty-nine patients recruited from the Miami Veterans Affairs eye clinic. Methods: The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-Eye) was completed to calculate a NPSI-Eye-Sub-Score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-Eye-Sub-Score with a significance threshold of P 0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were matrix metalloproteinase-19 (MMP19) (P = 1.12 × 10−5), zinc finger RNA-binding motif and serine/arginine rich-1 (ZRSR1) (P = 1.48 × 10−4), CTC-487M23.8 (P = 1.79 × 10−4), receptor expression-enhancing protein-5 (REEP5) (P = 2.36 × 10−4), and signal recognition particle-19 (SRP19) (P = 2.56 × 10−4). From gene set enrichment analysis, the sensory perception (false discovery rate = 6.57 × 10−3) and olfactory signaling (false discovery rate = 1.63 × 10−2) pathways were enriched with the most significant genes. Conclusions: Our GWAS revealed genes with protein products that may impact sensory perception, lending biological plausibility to a role for SNPs identified by our GWAS in the development of NOP. A better understanding of the biological relevance of these genes and pathways in the pathophysiology associated with NOP may facilitate future novel mechanism-based treatments. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords

• Neuropathic ocular pain
• Ocular pain
• Dry eye
• Dry eye disease
• Genome-wide association study