Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

ABSTRACT

Purpose: Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases. Methods: A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90. Results: Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3 rs2300163, EYA1 rs1077435, ASS1 rs141365191, and CHTF8 rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1 rs12622211, RXRA-COL5A1 rs3118515, rs3132306, rs1536482, rs3118520, KAT6B rs192187772, RAP2A-IPO5 rs41361245) were observed to be associated with CCT, and one SNP (USP13 rs6767552) was found to be associated with Km. Conclusions: In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.