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. Ace Therapeutics provides 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.
POAG Genetic Associations with CCT
The cornea, the outermost transparent layer of the eye, is the key ocular structure that focuses light onto the retina. Because of the large refractive power of the cornea, any structural changes to it may adversely affect vision. CCT is a morphological feature of the cornea and many studies have shown that thin CCT is associated with a variety of ocular diseases, including an association with an increased risk of POAG and an important endophenotype of POAG.
POAG is usually characterized by elevated IOP and results in optic nerve damage and vision loss. CCT is a key factor in the pathogenesis of POAG, as changes in CCT affect the accuracy of IOP measurements, with a decrease in CCT leading to an underestimation of IOP and the opposite with an increase in CCT. For this reason, the study of genetic factors affecting CCT is important to understand the underlying mechanisms of glaucoma.
Research Samples and Gene Selection
- Research samples. We carry out studies by animal testing, using biological samples such as mice and study protocols that adhere to animal use and ethics committee guidelines. Control samples such as healthy and glaucoma, male and female, are set up, central corneal sections are collected, stained for observation, microscopically photographed for imaging and CCT is measured.
- Gene selection. To identify and provide multiple loci associated with CCT, including ZNF469, COL5A1/RXRA, COL8A2, LOX, FBN2, SPRY2, CRIM1, AKAP13, FAM53B, FOXO1, IBTK and LRRK1, by analyzing regional SNP data from existing GWAS datasets and novel locus to determine POAG association of candidate genes.
Service Process
Our service uses a large sample of GWAS to identify novel loci for CCT associated with POAG by analyzing SNP data from the GWAS to identify candidate genes, containing SNPs within small intervals for each candidate.
Fig. 1 Service flow for SNP analysis associated with CCT.
- GWAS analysis. The association between genotype and CCT is analyzed by software calculation correction.
- SNP analysis. This includes genotyping and genotype interpolation, analysis to estimate candidate SNPs associated with POAG at genome-wide significance levels, SNPs as covariates in regression models for conditional association analysis and SNP-based heritability and variance interpretation.
- Genomic association assessment. Gene and pathway-based analyses.
Ace Therapeutics has the ability of GWAS to identify genes associated with CCT, contributing to the genetic exploration of glaucoma pathology by expanding genomic coverage and exploring new CCT-associated SNPs.
If you require specialist services for glaucoma research, please contact us for a professional glaucoma research program and tailored service offerings.
References
- Benson M D, et al. A targeted approach to genome-wide studies reveals new genetic associations with central corneal thickness. Mol Vis, 2017, 23:952-962.
- Choquet H, et al. A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness. Commun Biol, 2020, 3, 301.