Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

Genes (Basel). 2020 Dec 31;12(1):55. doi: 10.3390/genes12010055.


Glaucoma, the world's leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.

Keywords: exfoliation syndrome; exfoliative glaucoma; genetic/polygenic risk score; genetics; genome-wide association study; glaucoma; primary angle-closure glaucoma; primary open-angle glaucoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adult
  • Aged
  • Asian People
  • Black People
  • Exfoliation Syndrome / ethnology
  • Exfoliation Syndrome / genetics*
  • Exfoliation Syndrome / pathology
  • Eye Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Glaucoma, Angle-Closure / ethnology
  • Glaucoma, Angle-Closure / genetics*
  • Glaucoma, Angle-Closure / pathology
  • Glaucoma, Open-Angle / ethnology
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / pathology
  • Hispanic or Latino
  • Humans
  • Intraocular Pressure
  • Male
  • Multifactorial Inheritance
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Genetic
  • Risk Factors
  • White People


  • Eye Proteins
  • Nerve Tissue Proteins