Abstract
BackgroundThe genetic architecture underlying central cornea thickness (CCT) is far from understood. Most of the CCT-associated variants are located in the non-coding regions, raising the difficulty of following functional characterizations. Thus, integrative functional analyses on CCT-associated loci might benefit in overcoming these issues by prioritizing the hub genes that are located in the center of CCT genetic network.MethodsIntegrative analyses including functional annotations, enrichment analysis, and protein-protein interaction analyses were performed on all reported CCT GWAS lead SNPs, together with their proxy variants. Functional annotations were conducted by CADD, GWAVA, and Eigen. Enrichment analyses for CCT-associated genes were performed using ToppGene suite. Protein-protein interaction network and gene co-expression analyses were performed by GeneMANIA.ResultsFunctional annotations prioritized eight genes (ADAMSTS6, ARID5B, FOXO1, AKAP13, COL4A3, COL8A2, TBL1XR1, and KCMB2) harboring SNPs with strong evidence of regulatory potential. It was also shown that CCT-associated genes were significantly enriched in collagen-related pathways and the phenotype of keratoconus, and some of them were found to be involved in one interaction network.ConclusionThis study revealed the hub genes that were located in the center of CCT genetic network and provided a new insight into the genetic regulation underlying CCT GWAS findings.
Highlights
The cornea is a highly collagenous, transparent tissue through which light reaches the interior structures of the eye
Epidemiologic studies have shown that central cornea thickness (CCT) values differ among ethnic groups, with Europeans have higher CCT values than Africans, and Asians have a broad variation in CCT [1]
Our study demonstrated the potential of data integration to identify regulatory variants in CCT genome wide association studies (GWAS) findings, and highlighted the collagen and extracellular matrix pathways in the regulation of CCT
Summary
The cornea is a highly collagenous, transparent tissue through which light reaches the interior structures of the eye. Corneal thickness is closely related to corneal refractive power, which contributes to normal vision. Epidemiologic studies have shown that central cornea thickness (CCT) values differ among ethnic groups, with Europeans have higher CCT values than Africans, and Asians have a broad variation in CCT [1]. There have been growing evidences suggested that changes in CCT are closely related to ocular abnormalities. The genetic architecture underlying central cornea thickness (CCT) is far from understood. Most of the CCT-associated variants are located in the noncoding regions, raising the difficulty of following functional characterizations. Integrative functional analyses on CCT-associated loci might benefit in overcoming these issues by prioritizing the hub genes that are located in the center of CCT genetic network
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