{"doi":"10.1016/j.xops.2023.100384","title":"Genome Wide Association Study of Neuropathic Ocular Pain","abstract":"ABSTRACTPurposeTo 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.DesignProspective study of individuals with NOP.Participants329 patients recruited from the Miami Veterans Affairs eye clinic.MethodsThe 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<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] of GWAS online platform). The 13,865,778 single nucleotide polymorphisms (SNPs) from our GWAS analysis were mapped to 10,834 protein coding genes, and significant genes were run through gene set enrichment analysis (GSEA).Main Outcome MeasuresIdentification of SNPs and protein products that may be associated with the development of NOP.Results171 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 of P<5x10-8. This lead SNP, rs140293404 (P=1.23x10-8), is an intronic variant found within gene ENSG00000287251 coding for transcript ENST00000662732.1. Rs140293404 is in linkage disequilibrium with exon variant rs7926353 (r2>0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were MMP19 (P=1.12x10-5), ZRSR1 (P=1.48x10-4), CTC-487M23.8 (P=1.79x10-4), REEP5 (P=2.36x10-4), and SRP19 (P=2.56x10-4). From GSEA, the sensory perception (false discovery rate [FDR]=6.57x10-3) and olfactory signaling (FDR=1.63x10-2) pathways were enriched with the most significant genes.ConclusionOur 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. ABSTRACT 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. Prospective study of individuals with NOP. 329 patients recruited from the Miami Veterans Affairs eye clinic. 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<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] of GWAS online platform). The 13,865,778 single nucleotide polymorphisms (SNPs) from our GWAS analysis were mapped to 10,834 protein coding genes, and significant genes were run through gene set enrichment analysis (GSEA). Identification of SNPs and protein products that may be associated with the development of NOP. 171 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 of P<5x10-8. This lead SNP, rs140293404 (P=1.23x10-8), is an intronic variant found within gene ENSG00000287251 coding for transcript ENST00000662732.1. Rs140293404 is in linkage disequilibrium with exon variant rs7926353 (r2>0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were MMP19 (P=1.12x10-5), ZRSR1 (P=1.48x10-4), CTC-487M23.8 (P=1.79x10-4), REEP5 (P=2.36x10-4), and SRP19 (P=2.56x10-4). From GSEA, th","journal":"Ophthalmology Science","year":2023,"id":364357,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7854,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":227348,"name":"Daniel A. Rodriguez","orcid":"0000-0001-7682-6106","position":1,"is_corresponding":false},{"id":372942,"name":"Susan H. Slifer","orcid":null,"position":2,"is_corresponding":false},{"id":40736,"name":"Eden R. Martin","orcid":"0000-0002-4035-9152","position":3,"is_corresponding":false},{"id":725674,"name":"Roy C. Levitt","orcid":"0000-0002-6168-2274","position":4,"is_corresponding":false},{"id":288335,"name":"Anat Galor","orcid":"0000-0002-3026-6155","position":5,"is_corresponding":false},{"id":1054573,"name":"Jaxon J. Huang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:14:36.728255Z","pmid":"37868788","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}