A genome-wide association study for corneal curvature identifies the platelet-derived growth factor receptor alpha gene as a quantitative trait locus for eye size in white Europeans

Jeremy A. Guggenheim*, George McMahon, John P. Kemp, Saeed Akhtar, Beate St Pourcain, Kate Northstone, Susan M. Ring, David M. Evans, George Davey Smith, Nicholas J. Timpson, Cathy Williams

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

30 Citations (Scopus)


Purpose: Corneal curvature is a key determinant of the refractive power of the eye. Variants in two genes, FKBP12-rapamycin complex-associated protein 1 (FRAP1) on chromosome 1p36.2 and platelet-derived growth factor receptor alpha (PDGFRA) on chromosome 4q12, have shown genome-wide significant association with normal variation in corneal curvature in a study of subjects of Asian origin. Variants at the PDGFRA locus have also shown genome-wide significant association with corneal astigmatism. Whether these variants influence other ocular parameters such as axial length has yet to be reported. We performed a genome-wide association study for corneal curvature in white European subjects from a population-based birth cohort, with the aim of replicating and extending the above findings.

Methods: White European children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were examined at age about 15.5 years (95% confidence interval=15.45 to 15.48 years). Radius of corneal curvature and axial eye length were measured with an IOLmaster. DNA samples were genotyped with Illumina Human-Hap550 arrays and untyped variants imputed using MACH, with CEU individuals from HapMap release 22, Phase II NCBI B36, Single Nucleotide Polymorphism database 126 as the reference panel. Association between corneal curvature and single nucleotide polymorphism (SNP) genotype was tested, genome-wide, using mach2qtl, with sex as a covariate (n=2023; 46.6% male).

Results: The variant exhibiting the strongest evidence for association with corneal curvature (rs6554163; p=2.8x10(-6)) was located in the same linkage disequilibrium block as the previously discovered PDGFRA variants. Meta-analysis of the current and prior findings enhanced the evidence for association (rs17084051, p=4.5x10(-14)). rs6554163 genotype predicted 1.0% of variation in corneal curvature. In addition, these PDGFRA variants were associated with axial eye length, predicting 0.6% of the normal trait variation (p=5.3x10(-4)). Each copy of the minor allele of variants at the locus also increased the risk of corneal astigmatism in this white European cohort (odds ratio [OR]=1.24, 95% confidence interval=1.07-1.45; p=0.006).

Conclusion: As in Asians, variants at the PDGFRA locus influence corneal curvature (and corneal astigmatism). However, rather than affecting corneal curvature in isolation, this locus influences the size of the eye while maintaining its scaling.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalMolecular Vision
Publication statusPublished - 3 Jan 2013



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