Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma

We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG). Case-control genetic association study. Japanese POAG patients (n = 505) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (non-IOP–related genetic variants). The total number of risk alleles of the 17 IOP-related and 5 non-IOP–related genetic variants were calculated as the genetic risk score (GRS), and the associations between the GRS and family history of glaucoma as an indicator of POAG onset and age at the diagnosis of glaucoma as an indicator of POAG progression were evaluated. There was a significant association (P = .014; odds ratio 1.26 per GRS) between the non-IOP–related GRS, but not IOP-related GRS, and a family history of glaucoma in POAG. As the non-IOP–related GRS increased, the risk of a family history of glaucoma increased. In contrast, a significant association (P = .0014; β = −0.14) was found between the IOP-related GRS, but not non-IOP–related GRS, and age at the diagnosis of glaucoma. As the IOP-related GRS increased, age at the diagnosis of glaucoma decreased. The results indicate that non-IOP–related (optic nerve vulnerability) rather than IOP-related (IOP elevation) genetic variants may play an important role in the onset of POAG (family history of glaucoma) and that IOP-related rather than non-IOP–related genetic variants may play an important role in its progression (age at the diagnosis of glaucoma). •Phenotypes were evaluated using the genetic risk score of primary open-angle glaucoma.•Non-intraocular pressure–related genetic variants are associated with family history.•Intraocular pressure–related genetic variants are associated with age at diagnosis.•Non-intraocular pressure–related genetic variants play an important role in onset.•Intraocular pressure–related genetic variants play an important role in progression.