Genetic variants near PDGFRA are associated with corneal curvature in Australians

Invest Ophthalmol Vis Sci. 2012 Oct 11;53(11):7131-6. doi: 10.1167/iovs.12-10489.

Abstract

Purpose: Irregularity in the corneal curvature (CC) is highly associated with various eye disorders such as keratoconus and myopia. The sample had limited power to find genomewide significant (5 × 10(-8)) hits but good power for replication. Thus, an attempt was made to test whether alleles in the FRAP1 and PDGFRA genes, recently found to be associated with CC in Asian populations, also influence CC in Australians of North European ancestry. Results of initial genomewide association studies (GWAS) for CC in Australians were also reported.

Methods: Two population-based cohorts of 1788 Australian twins and their families, as well as 1013 individuals from a birth cohort from Western Australia, were genotyped using genomewide arrays. Following separate individual analysis and quality control, the results from each cohort underwent meta-analysis.

Results: Meta-analysis revealed significant replication of association between rs2114039 and corneal curvature (P = 0.0045). The SNP rs2114039 near PDGFRA has been previously implicated in Asians. No SNP at the FRAP1 locus was found to be associated in our Australian samples. No SNP surpassed the genomewide significance threshold of 5 × 10(-8). The SNP with strongest association was rs2444240 (P = 3.658 × 10(-7)), which is 31 kb upstream to the TRIM29 gene.

Conclusions: A significant role of the PDGFRA gene in determining corneal curvature in the Australian population was confirmed in this study, also highlighting the putative association of the TRIM29 locus with CC.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Cornea / anatomy & histology
  • Cornea / physiology*
  • Female
  • Genetic Variation / genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Infant, Newborn
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Refraction, Ocular / genetics*
  • Refractive Errors / genetics*
  • Western Australia
  • Young Adult

Substances

  • Receptor, Platelet-Derived Growth Factor alpha