Clinical Implications of the Novel Genetic Polymorphism Associated With Retinal Vein Occlusion: The East Asian GWAS Survey in a Single-Center Taiwanese Cohort

Purpose: To explore the single-nucleotide polymorphic features in an East Asian cohort of retinal venous occlusion (RVO) patients, to map pathogenic genes, and to analyze potential pathophysiological associations. Methods: This was a cross-sectional monocentric cohort study involving 172 patients with RVO and 1720 control participants from the Taiwanese population from a single center, Taichung Veterans General Hospital, under the framework of the Taiwan Precision Medicine Initiative (TPMI). DNA samples were collected from a Taiwanese population under the framework of the TPMI. Single nucleotide polymorphism (SNP) exploration was performed using PLINK 2.0. Gene mapping for the selected SNPs and functional analysis were conducted via the SNPXplorer online platform with the R packages biomaRt and clusterProfiler. Single-cell transcriptome mapping was achieved using the published Human Eye Transcriptome Atlas. Results: We report several novel RVO-associated SNPs with suggestive genome-wide association (P < 1 × 10-5), including rs16938701 (STAU2), rs76802456 (FAM189A1), rs995014 (N6AMT1), rs933813, rs6991412 (STAU2), rs79040889, and rs12524176. Among them, the STAU2 single-nucleotide variant, rs16938701, had the most remarkable association (P = 3.19 × 10-7). After mapping to the published human retina single-cell transcriptome atlas, STAU2 exhibited relatively high expression levels in retinal pigment epithelium/choroid complex, microglia, and hyalocyte among all ocular cell types. Conclusions: We identified several novel risk loci significantly associated with the occurrence of RVO and examined potential mechanistic links between specific biological processes and the pathophysiology of RVO. Translational Relevance: These findings provide novel insights into the genetic basis of RVO and highlight key pathways that may inform future research and therapeutic strategies.