Abstract:Primary glaucoma is a group of blinding eye diseases with high genetic heterogeneity, mainly comprising primary congenital glaucoma (PCG), primary open-angle glaucoma (POAG), and primary angle-closure glaucoma (PACG). PCG is mainly caused by recessive mutations in genes such as CYP1B1 and LTBP2, and is classified as a Mendelian disorder; however, it exhibits incomplete penetrance and regulation by modifier genes. In contrast, POAG and PACG are polygenic complex diseases. In POAG, rare high-penetrance variants in MYOC, OPTN, and TBK1 account for a small fraction of families, whereas most patients show an accumulation of small-effect variants involving endophenotypes such as intraocular pressure (IOP), cup-to-disc ratio (CDR), central corneal thickness (CCT). PACG is closely associated with genes related to anterior segment anatomical structures, including ABCC5, COL11A1, and PCMTD1-ST18. Both diseases are influenced by gene-environment interactions. Genome-wide association studies (GWAS), next-generation sequencing, and multi-omics technologies have identified numerous susceptibility loci and enhanced the clinical value of EPs and polygenic risk scores (PRS), laying the foundation for molecular diagnosis, risk stratification, and targeted therapy. In the future, integrating multi-omics and clinical imaging data, optimizing genetic risk prediction, and improving relevant ethical standards will promote the realization of precision medicine for primary glaucoma.
