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

PLoS Genet. 2011 Dec;7(12):e1002402. doi: 10.1371/journal.pgen.1002402. Epub 2011 Dec 1.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asia
  • Astigmatism / genetics*
  • Astigmatism / pathology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Corneal Diseases / genetics*
  • Corneal Diseases / pathology
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Refractive Errors / genetics*
  • Refractive Errors / pathology

Substances

  • Receptor, Platelet-Derived Growth Factor alpha