Genetics of primary open-angle glaucoma and its endophenotypes

Abstract

Glaucoma is a neurodegenerative disorder characterized by the loss of retinal ganglion cells and optic nerve fibers, resulting in the loss of visual field. Primary open-angle glaucoma (POAG) is the most prevalent subtype of glaucoma. Recent genome-wide association studies (GWASs) identified more than 100 variants associated with POAG and multiple loci associated with endophenotypes including the disc area, vertical cup-to-disc ratio (VCDR), and intraocular pressure (IOP). Especially, several GWASs reported the association between VCDR and variants near CDKN2B/CDKN2B-AS1, ATOH7, and CHEK2, and between IOP and variants near TMCO1, CAV1/CAV2, GAS7, and ARHGEF12. However, the effect of each variant on endophenotypes is modest; therefore, it is useful to construct a genetic risk score (GRS) based on the effect on endophenotypes by combining susceptible genetic variants. Several studies demonstrated that higher GRS was closely associated with endophenotypes including the VCDR, IOP, and age of diagnosis. Henceforth, by quantifying GRS, identification of high risk group before the disease onset, prediction of visual prognosis and early intervention may be possible.

Keywords: Endophenotypes; Genetic risk score; Genome-wide association studies; Intraocular pressure; Primary open-angle glaucoma; Vertical cup-to-disc ratio.