title: Genetic investigation into the endophenotypic status of central corneal thickness and optic disc parameters in relation to open-angle glaucoma.
abstract: OBJECTIVE
  To ascertain if single nucleotide polymorphisms (SNPs) involved in the determination of central corneal thickness, optic disc area, and vertical cup-to-disc ratio (VCDR) also are associated with open-angle glaucoma (OAG).
  
  
  METHODS
  Retrospective case-control genetic association study.
  
  
  METHODS
  A total of 16 SNPs associated with central corneal thickness, optic disc area, and VCDR were genotyped in 876 OAG cases and 883 normal controls. To determine if the SNPs were also correlated with OAG severity, the cohort was stratified into advanced OAG (n = 326) and nonadvanced OAG (n = 550). Both the cases and controls were of European descent and were recruited from within Australia.
  
  
  RESULTS
  Two VCDR SNPs were found to be significantly associated with OAG after correction for multiple testing. The 2 SNPs were rs10483727, found adjacent to the SIX1 gene (P = 6.2 × 10(-06); odds ratio, 1.38; 95% confidence interval, 1.20 to 1.59), and rs1063192, found within the CDKN2B gene (P = 2.2 × 10(-05); odds ratio, 0.74; 95% confidence interval, 0.64 to 0.85). The CDKN2B variant rs1063192 also was found to be associated more strongly with advanced OAG.
  
  
  CONCLUSIONS
  The findings from this study indicate that variants influencing VCDR are also risk alleles for OAG in our Australian cohort of European descent. The identification of SIX1 and CDKN2B as susceptibility loci will assist in understanding the pathologic mechanisms involved in the development of OAG.
authors: Department of Ophthalmology, Flinders University, Adelaide, Australia.
authors: David P
authors: DP
authors: Dimasi
authors: Kathryn P
authors: KP
authors: Burdon
authors: Alex W
authors: AW
authors: Hewitt
authors: Jude
authors: J
authors: Fitzgerald
authors: Jie Jin
authors: JJ
authors: Wang
authors: Paul R
authors: PR
authors: Healey
authors: Paul
authors: P
authors: Mitchell
authors: David A
authors: DA
authors: Mackey
authors: Jamie E
authors: JE
authors: Craig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D016022:Case-Control Studies; D003315:Cornea / Q000473:pathology*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D058068:Endophenotypes; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012189:Retrospective Studies; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018398:Homeodomain Proteins; C099236:SIX1 protein, human