title: Association of open-angle glaucoma loci with incident glaucoma in the Blue Mountains Eye Study.
abstract: OBJECTIVE
  To determine if open-angle glaucoma (OAG)-associated single nucleotide polymorphisms (SNPs) are associated with incident glaucoma and if such genetic information is useful in OAG risk prediction.
  
  
  METHODS
  Case-control from within a population-based longitudinal study.
  
  
  METHODS
  study population: Individuals aged over 49 years of age living in the Blue Mountains region west of Sydney and enrolled in the Blue Mountains Eye Study. observation: Cases for this sub-study (n = 67) developed incident OAG between baseline and 10-year visits, in either eye, while controls (n = 1919) had no evidence for OAG at any visit. All participants had an ocular examination and DNA genotyped for reported OAG risk SNPs. main outcome measure: Incident OAG.
  
  
  RESULTS
  Two loci also known to be associated with cup-to-disc ratio as well as OAG (9p21 near CDKN2B-AS1 and SIX1/SIX6) were both significantly associated with incident OAG in the Blue Mountains Eye Study cohort (P = .006 and P = .004, respectively). The TMCO1 locus was nominally associated (P = .012), while the CAV1/CAV2 and 8q22 loci were not associated. Multivariate logistic regression and neural network analysis both indicated that the genetic risk factors contributed positively to the predictive models incorporating traditional risk factors.
  
  
  CONCLUSIONS
  This study shows that previously reported genetic variations related to OAG and cup-to-disc ratio are associated with the onset of OAG and thus may become useful in risk prediction algorithms designed to target early treatment to those most at risk of developing glaucoma.
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia. Electronic address: Kathryn.burdon@utas.edu.au.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Lee
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Healey
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia; Save Sight Institute, University of Sydney, Sydney, Australia.
authors.forename: Andrew J R
authors.initials: AJ
authors.lastname: White
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Rochtchina
authors.affiliation: Save Sight Institute, University of Sydney, Sydney, Australia; Department of Ophthalmology, Ipswich Hospital, Ipswich, United Kingdom.
authors.forename: Peter B M
authors.initials: PB
authors.lastname: Thomas
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009517:New South Wales / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests