ReviewClinical ophthalmology (Auckland, N.Z.)2026
Genetic Architecture and Clinical Phenotypes of Primary Open-Angle Glaucoma: An Updated Review of Mendelian Genes, GWAS Loci, and Polygenic Risk.
Review in Clinical ophthalmology (Auckland, N.Z.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To synthesize the genetic architecture of primary open-angle glaucoma (POAG) across the full variant spectrum and map each genetic subtype to its clinical phenotype, IOP profile, optic nerve morphology, systemic associations, and treatment response. Methods: PubMed/MEDLINE was searched from inception through April 2025 for POAG genetics, susceptibility genes, GWAS loci, polygenic risk scores, and gene-specific clinical correlations. Eligible designs included peer-reviewed original research, GWAS meta-analyses, candidate-gene studies, family-based linkage analyses, cohort and case-control studies, and PRS development in human subjects. Genetic association studies were appraised using Q-Genie; observational clinical studies were appraised using the Newcastle-Ottawa Scale. Results: Seven high-penetrance Mendelian genes (MYOC, OPTN, TBK1, WDR36, NTF4, FOXC1, CYP1B1) account for fewer than 10% of cases, each defining a clinically distinct subtype: juvenile high-tension glaucoma (MYOC), normal-tension neurodegeneration (OPTN, TBK1), and syndromic developmental glaucoma (FOXC1, CYP1B1). GWAS meta-analyses have identified 100 to 127 susceptibility loci converging on five biological axes: trabecular meshwork dysfunction, retinal ganglion cell survival, autophagy and protein homeostasis, neuroinflammation, and extracellular matrix integrity. Polygenic risk scores combined with clinical variables achieve an AUC of 0.89. Conclusion: POAG comprises genetically and clinically distinct subtypes defined by dominant molecular axes. Gene-specific data reveal actionable pharmacogenomic signals: ROCK inhibitors for ARHGEF12 and AFAP1 carriers, nicotinamide for OPTN and TXNRD2 subtypes, and goniotomy for CYP1B1-associated congenital glaucoma. IOP-centric management is insufficient for normal-tension subtypes driven by autophagy failure and neuroinflammation. The framework supports genotype-guided decisions on screening intensity, IOP targets, and neuroprotective adjuncts.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.