Primary open-angle glaucoma (POAG) is the most common form of glaucoma, and known risk factors for POAG include advanced age, high intraocular pressure (IOP), reduced central corneal thickness (CCT), and high myopia. In past studies, genome-wide association studies (GWAS) have successfully identified dozens of single nucleotide polymorphisms (SNPs) associated with POAG and related endophenotypes.
Fig. 1 Genes associated with POAG and endophenotype. (Iglesias A, et al., 2015)
The figure above lists variants of optic disc parameters associated with POAG that have been identified in GWAS so far, such as VCDR, CA, DA, and variants of IOP and CCT. However, GWAS research can continue to expand, and expanding the sample size and study population can help us to identify new variants of interest. With improved technology and innovative solutions, Ace Therapeutics provides our clients POAG's GWAS services to identify new SNPs for different endophenotypes, including IOP, CA, DA, VCDR, CCT and other association studies of interest, and to fully explore the mechanisms of glaucoma.
Services for Genome-Wide Association Studies with POAG
IOP is controlled by balancing atrial aqueous production from the ciliary body with drainage of the drainage structures, and when atrial aqueous drainage is inefficient it can lead to an increase in IOP, which is an important risk factor for the development of POAG and can be used as a measurable endophenotype closely related to the disease phenotype, with genome-wide association studies (GWAS) to identify disease-associated genetic variants.
The optic nerve head has a normal physiological depression called the optic cup, which is like a cup. It has a normal proportion in the optic nerve head, if it is large, there is a possibility of glaucoma or other congenital myopia. Cup area (CA) is an optic nerve parameter and a POAG endophenotype with high heritability. GWAS can help identify multiple loci associated with CA and POAG.
The important endophenotypes of POAG include optic disc-related parameters that are measurable characteristics, including optic disc area (DA). The genetic component of endophenotypes is usually quantified by heritability, and DA has a heritability of 0.72, which is among the higher POAG-related endophenotypes with high heritability. DA contributes to the genetic power of glaucoma, and its study can help dissect POAG, which is complex and has diverse endophenotypes.
The optic disc is located at the back of the eye where the optic nerve is formed. The vertical cup to disc ratio (VCDR), which is the ratio of the vertical diameter of the optic cup to the vertical diameter of the optic disc, can often be used to characterize the degree of depression of the optic disc and is an important endophenotype of POAG. And POAG mechanisms may be better elucidated by identifying factors that influence individual quantitative traits, such as VCDR.
Central corneal thickness (CCT) is a highly heritable ocular feature and many studies have demonstrated that CCT plays an important role in ocular health and is an important risk factor that can influence POAG. We provide GWAS research services to identify CCT-associated variants, with controlled analysis of SNPs across the genome to determine if there are genes associated with CCT.
GWAS
GWAS is designed to genotype SNPs across the genome based on a POAG/control study, to tag relevant SNPs in candidate genomic regions and to analyze pathways associated with causing POAG.
Applications
- Our research service reveals new pathways and biological mechanisms through GWAS, and the identified genetic variants open new perspectives for understanding known potential pathways in the pathogenesis of POAG.
Ace Therapeutics is committed to discovering new variants to advance POAG research at the molecular level, and we look forward to your innovative glaucoma projects, please contact us for collaboration.
Reference
- Iglesias A, et al. Genes, pathways, and animal models in primary open-angle glaucoma. Eye, 2015, 29:1285–1298.