ArticleMedicine2026
Genetic associations of variants in 10 glaucoma-related genes with POAG risk and structural phenotypes in Korean subjects.
Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
While a few studies have reported on single nucleotide polymorphisms associated with glaucoma in the Korean population, comprehensive data on genotype-phenotype correlations across multiple candidate genes are lacking. This study aimed to investigate the associations of variants in 10 candidate genes (CDKN2B, SIX1, SIX6, SCYL1, CHEK2, ATOH7, DCLK1, RERE, CDC7, and CARD10) with primary open-angle glaucoma (POAG) susceptibility and structural phenotypic features. We employed a 2-stage study design consisting of a discovery phase (targeted sequencing of 100 subjects) and a confirmation phase (genotyping of 24 selected variants in a total cohort of 382 subjects: 160 POAG cases and 222 controls). Associations with POAG risk and structural parameters, including vertical cup-to-disc ratio and retinal nerve fiber layer thickness (RNFLT), were analyzed using multivariable logistic regression and analysis of variance. The Benjamini-Hochberg false discovery rate method was applied to account for multiple testing. Regarding POAG susceptibility, 3 variants in DCLK1, SIX6, and SCYL1 showed nominal significance in the initial analysis but did not withstand false discovery rate correction. However, regarding phenotypic traits, rs33912345 in SIX6 demonstrated robust significant associations with both increased vertical cup-to-disc ratio and reduced average, superior, temporal and inferior RNFLT. Additionally, rs748189671 in RERE was significantly associated with temporal RNFLT. In detailed clock-hour analysis, variants in DCLK1 and SIX1 also showed significant correlations with 3 o'clock sector of RNFLT. Our findings identify DCLK1, SIX1, SIX6 and RERE as key genetic factors influencing optic nerve morphology and RNFLT in the Korean population. These results suggest that these genes may primarily modulate the structural vulnerability of the optic nerve, highlighting their potential utility for phenotypic profiling of glaucoma in the Korean population. However, these results are exploratory, and further large-scale studies are warranted to validate these associations and elucidate their clinical implications in glaucoma genetics.
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