Genome-Wide Association Study (GWAS) is a large scale case-control study and typically focus on association between single-nucleotide polymorphisms (SNPs) and traits. The approach of GWAS involves rapidly scanning SNPs across the entire genomes of a person to find genetic variations associated with a particular disease. As of 2011, almost 4000 SNPs were identified to be associated to over 200 diseases and traits examined by about 1200 human GWAS. In this paper, author focus on GWAS in glaucoma.

Glaucoma is a multifactorial neurodegenerative disease characterized by various clinical manifestations, involving degeneration of the optic nerve and loss of retinal ganglion cell (RGC) in retina. The elevated intraocular pressure (IOP) is a major risk factor and glaucoma is believed to be affected by other factors whose molecular effects are not well defined. The findings from GWAS in glaucoma provided a new insight to glaucoma research, and advanced our understanding of genetic factors that underlie glaucoma in following aspects.

(1) Identified new principal genetic factors in pathogenesis of exfoliation glaucoma. Two SNPs in exon 1 of LOXL1 gene were first identified and confirmed genetic susceptibility of LOXL1 polymorphisms to PEX syndrome/glaucoma worldwide.

(2) IOP elevation was associated with variants in GAS7 and TMCO1 genes, which were highly expressed in the ciliary body and TM as well as in the lamina cribrosa, optic nerve and retina.

(3) The variations in various genes contribute to development of glaucoma. The variations in CAV1 and CAV2 genes, for example, were involved in pathogenesis of POAG; common variants in SRBD1 and ELOVL5 in normal tension glaucoma; the VAV2/VAV3 -deficient mice showed early onset of iridocorneal angle changes and elevated IOP, and the variants in VAV2/VAV3 were identified in Japanese patients of POAG.

(4)Targeting early molecular events may provide effective new treatment for glaucoma. GWAS on DAB/2J mouse revealed the up-regulation of the complement cascade and the endothelin system at early stage of glaucoma. Inhibition of the endothelin showed the protective against glaucomatous damage.

In summary, GWAS equips a non-candidate-driven approach and increases the scope of glaucoma research.