A Novel Locus for Central Corneal Thickness on Chromosome 6q14.1

Abstract

Purpose: : Central corneal thickness (CCT) is a highly heritable trait which has been proposed to influence disorders of the anterior segment of the eye. Genes that control CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open angle glaucoma (POAG) and keratoconus. Here we describe a novel locus associated with central corneal thickness (CCT).

Methods: : We conducted two population-based GWAS for the CCT trait on 5080 individuals drawn from two Asian ethnic populations in Singapore: 2538 Indian subjects (Singapore Indian Eye Study [SINDI], and 2542 Malay subjects (the Singapore Malay Eye Study [SiMES]), aged 40 years and over. GWAS data for CCT of 906 individuals from the Blue Mountains Eye Study (BMES), Australia was used as the ‘replication’ sample for looking up significant associations. Formal threshold for genome-wide significance was defined as P < 5.0 x 10^-8.

Results: : Meta-analysis of SINDI and SiMES provided evidence of association exceeding genome-wide significance at 4 loci. These included a novel locus on Chromosome 6q14.1 (P = 4.62 x 10-8) and three others (ZNF469, COL8A2, and RXRA-COL5A1) described previously. Further evidence of association for the chromosome 6 locus was observed in the individuals of the BMES (P = 0.029). A joint analysis of all samples strongly supported the CCT locus on chromosome 6 (meta-P = 4.08 x 10^-9).

Conclusions: : Discovery of genes that control CCT not only offer mechanistic insights into the regulation of CCT but also offers candidate genes for interrogation for POAG and keratoconus.

Keywords: gene mapping • cornea: clinical science • genetics