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

Heritability of corneal curvature and astigmatism - A videokeratographic child-parent comparison study

PURPOSE: To study child-parent similarities and the heritability of corneal shape by applying a variance component model to videokeratographic data. METHODS: Sixteen astigmatic (keratometric cylinder >/= 1.0 D) and 18 nonastigmatic (keratometric cylinder < 1.0 D) children, 7-14 years of age (mean age, 9.5 years), were enrolled with their parents. Corneal curvature, corneal astigmatism (axis and magnitude), asphericity, corneal uniformity index, and Rabinowitz McDonnell inferior-superior dioptric asymmetry value (I-S value), as well as spherical and astigmatic topographic patterns, were determined by a corneal topographer. Child-parent comparisons were assessed through a 1-way analysis of variance and the chi test. For corneal curvature, corneal astigmatism, and asphericity, heritability was estimated by a variance component model after adjustments were made for age and sex. RESULTS: Both astigmatic and nonastigmatic children showed steeper keratometric values than their parents (P < 0.05). The axis values of corneal astigmatism showed no statistically significant difference (P = 0.684) between astigmatic offspring and their parents, whereas the magnitude values were significantly higher (P < 0.001) in astigmatic children. Altogether, 68% (95% confidence interval [CI], 66%-72%) of child-parent comparisons showed the same topographic pattern between parents and their offspring. Heritability values (48%; 95% CI, 36%-57%) were statistically significant for corneal curvature (P < 0.00001) and <30% for corneal astigmatism and asphericity. CONCLUSIONS: The application of a variance component model to videokeratographic child-parent comparisons suggests that the genetic contribution to corneal shape affects corneal curvature rather than corneal astigmatism