Genome-Wide Meta-Analysis of Five Asian Cohorts Identifies PDGFRA as a Susceptibility Locus for Corneal Astigmatism

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio = 1.26 (95% CI: 1.16–1.36), Pmeta = 7.87×10−9) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations. Author Summary: Corneal astigmatism is associated with reduced visual acuity and an increased risk of developing refractive amblyopia. Although it is highly heritable, there is no prior study on the genetic etiology of corneal astigmatism. Our genome-wide meta-analysis across 8,513 individuals in five genome-wide surveys from three genetically diverse populations in Asia reveals that genetic variants in the PDGFRA gene on chromosome 4q12 is significantly associated with corneal astigmatism. These polymorphisms in the PDGFRA gene exhibit strong and consistent effects over all five Asian cohorts. PDGFRA is a receptor for platelet-derived growth factor, which is expressed in many retinal tissues in the eyes and appears to contribute to ocular development. Results from our study further suggest the potential role of PDGFRA in the regulation of corneal biometrics.