Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for corneal astigmatism

Abstract

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), P(meta) = 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.

Figure 1. Regional plot of the association signals from the meta-analysis of the five GWAS cohorts around the PDGFRA gene locus.

A region of 400 kb around the lead SNP (rs7677751, red diamond) is shown. The LD between the lead SNP and the neighbouring SNPs is represented by the shading of the squares, with increasing shade of red indicating higher LD as measured by r². The blue lines represent the recombination rates of JPT+CHB panels from HapMap II.

Figure 2. Forest plot of the estimated allelic odds ratios for the lead SNP rs7677751.

The allelic odd ratios for allele T of rs7677751 and 95% confidence intervals are presented for the five studies separately (black rectangles for discovery studies, green rectangles for replication studies), the meta-analyses during the discovery (black diamond) and replication (green diamond) phases, and for the overall meta-analysis across all five studies (red diamond).