Genetics of Glaucoma

Abstract

A family history of glaucoma is a recognized disease risk factor, and recent studies suggest that glaucoma is one of the most heritable of all human diseases (Youngblood H, Hauser MA, Liu Y, Exp Eye Res 188: 107795, 2019; Wang K, Gaitsch H, Poon H, Cox NJ, Rzhetsky A, Nat Genet 49(9): 1319-1325, 2017). Glaucoma can be inherited as a Mendelian single gene disorder, caused by a single gene defect, or as a complex trait that results from the interactions of multiple genes and environmental factors. In general, the early-onset (childhood) forms of glaucoma are inherited as Mendelian autosomal dominant or recessive traits, while the adult-onset diseases are inherited as complex traits. Genes that predispose to glaucoma may influence intraocular pressure or degeneration of the optic nerve or both. The types of glaucoma inherited as Mendelian traits include juvenile open-angle glaucoma; congenital glaucoma; developmental glaucomas, including Rieger's syndrome and aniridia; and familial normal tension glaucoma (Lewis CJ, Hedberg-Buenz A, DeLuca AP, Stone EM, Alward WLM, Fingert JH, Hum Mol Genet 26(R1): R28-R36, 2017; Sears NC, Boese EA, Miller MA, Fingert JH, Exp Eye Res 186: 107702, 2019). Complex forms of glaucoma include pigmentary glaucoma, primary open-angle glaucoma, angle-closure glaucoma, and exfoliation glaucoma (Wiggs JL, Pasquale LR, Hum Mol Genet 26(R1): R21-R27, 2017.). Genes and loci identified for these forms of glaucoma are discussed.