Associations between Disc Hemorrhage and Primary Open-Angle Glaucoma Based on Genome-Wide Association and Mendelian Randomization Analyses

<b>Background/Objectives:</b> We aimed to investigate the genetic loci related to disc hemorrhage (DH) and the relationship of causation between DH and primary open-angle glaucoma (POAG) using a genome-wide association study (GWAS) in East Asian individuals. <b>Methods:</b> The GWAS included 8488 Koreans who underwent ocular examination including fundus photography to determine the presence of DH and POAG. We performed a GWAS to identify significant single-nucleotide polymorphisms (SNPs) associated with DH and analyzed the heritability of DH and genetic correlation between DH and POAG. The identified SNPs were utilized as instrumental variables (IVs) for two-sample Mendelian randomization (MR) analysis. The POAG outcome dataset was adopted from Biobank Japan data (n = 179,351). <b>Results:</b> We found that the rs62463744 (<i>TMEM270</i>;<i>ELN</i>), rs11658281 (<i>CCDC42</i>), and rs77127203 (<i>PDE10A</i>;<i>LINC00473</i>) SNPs were associated with DH. The SNP heritability of DH was estimated to be 6.7%, with an absence of a genetic correlation with POAG. MR analysis did not reveal a causal association between DH and POAG for East Asian individuals. <b>Conclusions:</b> The novel loci underlying DH in the Korean cohort revealed SNPs in the <i>ELN</i>, <i>CCDC41</i>, and <i>LINC00473</i> genes. The absence of a causal association between DH and POAG implies that DH is a shared risk factor, rather than an independent culprit factor, and warrants further investigation.