title: CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States.
abstract: OBJECTIVE
  To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.
  
  
  METHODS
  Retrospective observational case series.
  
  
  METHODS
  We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.
  
  
  RESULTS
  For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05).
  
  
  CONCLUSIONS
  Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. Louis_Pasquale@meei.harvard.edu
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Loomis
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.forename: Wael
authors.initials: W
authors.lastname: Abdrabou
authors.forename: Donald L
authors.initials: DL
authors.lastname: Budenz
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delbono
authors.forename: David S
authors.initials: DS
authors.lastname: Friedman
authors.forename: Douglas
authors.initials: D
authors.lastname: Gaasterland
authors.forename: Terry
authors.initials: T
authors.lastname: Gaasterland
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Grosskreutz
authors.forename: Richard K
authors.initials: RK
authors.lastname: Lee
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lichter
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Sayoko E
authors.initials: SE
authors.lastname: Moroi
authors.forename: Lana M
authors.initials: LM
authors.lastname: Olson
authors.forename: Tony
authors.initials: T
authors.lastname: Realini
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rhee
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.forename: Kuldev
authors.initials: K
authors.lastname: Singh
authors.forename: Douglas
authors.initials: D
authors.lastname: Vollrath
authors.forename: Gadi
authors.initials: G
authors.lastname: Wollstein
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000473:pathology; D009901:Optic Nerve Diseases / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D012189:Retrospective Studies; D014130:Trabeculectomy; D014481:United States; D014794:Visual Fields
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding