title: Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.
abstract: OBJECTIVE
  Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry.
  
  
  METHODS
  Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis.
  
  
  RESULTS
  Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009.
  
  
  CONCLUSIONS
  Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.
authors.affiliation: Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia. seyhanyazar@lei.org.au
authors.forename: Seyhan
authors.initials: S
authors.lastname: Yazar
authors.forename: Aniket
authors.initials: A
authors.lastname: Mishra
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kearns
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Mountain
authors.forename: Craig
authors.initials: C
authors.lastname: Pennell
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
mesh_terms: D001251:Astigmatism / Q000235:genetics*; D001315:Australia; D015331:Cohort Studies; D003315:Cornea / Q000473:pathology*; D003710:Demography; D005260:Female; D005789:Genealogy and Heraldry; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D018433:Twin Studies as Topic; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha