Functional relevance for central cornea thickness-associated genetic variants by using integrative analyses

Area of Science:

• Genomics
• Ophthalmology
• Bioinformatics

Background:

• The genetic basis of central cornea thickness (CCT) remains largely unknown.
• Non-coding variants associated with CCT pose challenges for functional studies.
• Integrative analysis can prioritize key genes within the CCT genetic network.

Purpose of the Study:

• To identify hub genes central to the genetic network of central cornea thickness.
• To gain insights into the genetic regulation of CCT using integrative functional analyses.

Main Methods:

• Performed functional annotations (CADD, GWAVA, Eigen), enrichment analyses (ToppGene), and protein-protein interaction analyses (GeneMANIA).
• Utilized genome-wide association study (GWAS) lead single nucleotide polymorphisms (SNPs) and their proxies for CCT.

Main Results:

• Prioritized eight genes (ADAMSTS6, ARID5B, FOXO1, AKAP13, COL4A3, COL8A2, TBL1XR1, KCMB2) with regulatory potential.
• Identified significant enrichment in collagen-related pathways and keratoconus.
• Revealed an interaction network involving CCT-associated genes.

Conclusions:

• Identified hub genes central to the CCT genetic network.
• Provided novel insights into the genetic regulation of CCT based on GWAS findings.