title: Evaluating the association between keratoconus and the corneal thickness genes in an independent Australian population.
abstract: OBJECTIVE
  A recent genome-wide association study (GWAS) identified six loci associated with central corneal thickness that also conferred associated risk of keratoconus (KC). We aimed to assess whether genetic associations existed for these loci with KC or corneal curvature in an independent cohort of European ancestry.
  
  
  METHODS
  In total, 157 patients with KC were recruited from public and private clinics in Melbourne, Australia, and 673 individuals without KC were identified through the Genes in Myopia study from Australia. The following six single-nucleotide polymorphisms (SNPs) that showed a statistically significant association with KC in a recent GWAS study were selected for genotyping in our cohort: rs4894535 (FNDC3B), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A), rs2721051 (FOXO1), and rs9938149 (BANP-ZNF469). The SNPs were assessed for their association with KC or corneal curvature using logistic or linear regression methods, with age and sex included as covariates. Bonferroni corrections were applied to account for multiple testing.
  
  
  RESULTS
  Genotyping data were available for five of the SNPs. Statistically significant associations with KC were found for the SNPs rs1324183 (P = 0.001; odds ratio [OR], 1.68) and rs9938149 (P = 0.010; OR, 1.47). Meta-analysis of previous studies yielded genome-wide significant evidence of an association for rs1324183, firmly establishing it as a KC risk variant. None of the SNPs were significantly associated with corneal curvature.
  
  
  CONCLUSIONS
  The SNPs rs1324183 in the MPDZ-NF1B gene and rs9938149 (between BANP and ZNF4659) were associated with KC in this independent cohort, but their association was via a non-corneal curvature route.
authors.affiliation: Ocular Genetics Unit, Centre for Eye Research Australia, East Melbourne, Australia.
authors.forename: Srujana
authors.initials: S
authors.lastname: Sahebjada
authors.forename: Maria
authors.initials: M
authors.lastname: Schache
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Grant
authors.initials: G
authors.lastname: Snibson
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
authors.forename: Mark
authors.initials: M
authors.lastname: Daniell
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D003315:Cornea / Q000378:metabolism / Q000473:pathology*; D019781:Corneal Topography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007640:Keratoconus / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
chemical_list: D005136:Eye Proteins
keywords: candidate genes; central corneal thickness; keratoconus