CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States

Louis R. Pasquale, Stephanie J. Loomis, Jae H. Kang, Brian L. Yaspan, Wael Abdrabou, Donald L. Budenz, Teresa C. Chen, Elizabeth Delbono, David S. Friedman, Douglas Gaasterland, Terry Gaasterland, Cynthia L. Grosskreutz, Richard K. Lee, Paul R. Lichter, Yutao Liu, Catherine A. McCarty, Sayoko E. Moroi, Lana M. Olson, Tony Realini, Douglas J. RheeJoel S. Schuman, Kuldev Singh, Douglas Vollrath, Gadi Wollstein, Donald J. Zack, R. Rand Allingham, Margaret A. Pericak-Vance, Robert N. Weinreb, Kang Zhang, Michael A. Hauser, Julia E. Richards, Jonathan L. Haines, Janey L. Wiggs

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Purpose: 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. Design: 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). Conclusion: 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.

Original languageEnglish (US)
JournalAmerican Journal of Ophthalmology
Volume155
Issue number2
DOIs
StatePublished - Jan 1 2013

Fingerprint

Glaucoma
Alleles
Genotype
Single Nucleotide Polymorphism
Intraocular Pressure
Cyclin-Dependent Kinase Inhibitor p15
National Eye Institute (U.S.)
Primary Open Angle Glaucoma
Antisense RNA
Nerve Degeneration
Untranslated RNA
DNA
Medical Genetics
Optic Nerve
Genes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Pasquale, L. R., Loomis, S. J., Kang, J. H., Yaspan, B. L., Abdrabou, W., Budenz, D. L., ... Wiggs, J. L. (2013). CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States. American Journal of Ophthalmology, 155(2). https://doi.org/10.1016/j.ajo.2012.07.023

CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States. / Pasquale, Louis R.; Loomis, Stephanie J.; Kang, Jae H.; Yaspan, Brian L.; Abdrabou, Wael; Budenz, Donald L.; Chen, Teresa C.; Delbono, Elizabeth; Friedman, David S.; Gaasterland, Douglas; Gaasterland, Terry; Grosskreutz, Cynthia L.; Lee, Richard K.; Lichter, Paul R.; Liu, Yutao; McCarty, Catherine A.; Moroi, Sayoko E.; Olson, Lana M.; Realini, Tony; Rhee, Douglas J.; Schuman, Joel S.; Singh, Kuldev; Vollrath, Douglas; Wollstein, Gadi; Zack, Donald J.; Allingham, R. Rand; Pericak-Vance, Margaret A.; Weinreb, Robert N.; Zhang, Kang; Hauser, Michael A.; Richards, Julia E.; Haines, Jonathan L.; Wiggs, Janey L.

In: American Journal of Ophthalmology, Vol. 155, No. 2, 01.01.2013.

Research output: Contribution to journalArticle

Pasquale, LR, Loomis, SJ, Kang, JH, Yaspan, BL, Abdrabou, W, Budenz, DL, Chen, TC, Delbono, E, Friedman, DS, Gaasterland, D, Gaasterland, T, Grosskreutz, CL, Lee, RK, Lichter, PR, Liu, Y, McCarty, CA, Moroi, SE, Olson, LM, Realini, T, Rhee, DJ, Schuman, JS, Singh, K, Vollrath, D, Wollstein, G, Zack, DJ, Allingham, RR, Pericak-Vance, MA, Weinreb, RN, Zhang, K, Hauser, MA, Richards, JE, Haines, JL & Wiggs, JL 2013, 'CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States', American Journal of Ophthalmology, vol. 155, no. 2. https://doi.org/10.1016/j.ajo.2012.07.023
Pasquale, Louis R. ; Loomis, Stephanie J. ; Kang, Jae H. ; Yaspan, Brian L. ; Abdrabou, Wael ; Budenz, Donald L. ; Chen, Teresa C. ; Delbono, Elizabeth ; Friedman, David S. ; Gaasterland, Douglas ; Gaasterland, Terry ; Grosskreutz, Cynthia L. ; Lee, Richard K. ; Lichter, Paul R. ; Liu, Yutao ; McCarty, Catherine A. ; Moroi, Sayoko E. ; Olson, Lana M. ; Realini, Tony ; Rhee, Douglas J. ; Schuman, Joel S. ; Singh, Kuldev ; Vollrath, Douglas ; Wollstein, Gadi ; Zack, Donald J. ; Allingham, R. Rand ; Pericak-Vance, Margaret A. ; Weinreb, Robert N. ; Zhang, Kang ; Hauser, Michael A. ; Richards, Julia E. ; Haines, Jonathan L. ; Wiggs, Janey L. / CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States. In: American Journal of Ophthalmology. 2013 ; Vol. 155, No. 2.
@article{588d01b7886b4d1a8ff463b1a92d7b1e,
title = "CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States",
abstract = "Purpose: 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. Design: 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). Conclusion: 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.",
author = "Pasquale, {Louis R.} and Loomis, {Stephanie J.} and Kang, {Jae H.} and Yaspan, {Brian L.} and Wael Abdrabou and Budenz, {Donald L.} and Chen, {Teresa C.} and Elizabeth Delbono and Friedman, {David S.} and Douglas Gaasterland and Terry Gaasterland and Grosskreutz, {Cynthia L.} and Lee, {Richard K.} and Lichter, {Paul R.} and Yutao Liu and McCarty, {Catherine A.} and Moroi, {Sayoko E.} and Olson, {Lana M.} and Tony Realini and Rhee, {Douglas J.} and Schuman, {Joel S.} and Kuldev Singh and Douglas Vollrath and Gadi Wollstein and Zack, {Donald J.} and Allingham, {R. Rand} and Pericak-Vance, {Margaret A.} and Weinreb, {Robert N.} and Kang Zhang and Hauser, {Michael A.} and Richards, {Julia E.} and Haines, {Jonathan L.} and Wiggs, {Janey L.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.ajo.2012.07.023",
language = "English (US)",
volume = "155",
journal = "American Journal of Ophthalmology",
issn = "0002-9394",
publisher = "Elsevier USA",
number = "2",

}

TY - JOUR

T1 - CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States

AU - Pasquale, Louis R.

AU - Loomis, Stephanie J.

AU - Kang, Jae H.

AU - Yaspan, Brian L.

AU - Abdrabou, Wael

AU - Budenz, Donald L.

AU - Chen, Teresa C.

AU - Delbono, Elizabeth

AU - Friedman, David S.

AU - Gaasterland, Douglas

AU - Gaasterland, Terry

AU - Grosskreutz, Cynthia L.

AU - Lee, Richard K.

AU - Lichter, Paul R.

AU - Liu, Yutao

AU - McCarty, Catherine A.

AU - Moroi, Sayoko E.

AU - Olson, Lana M.

AU - Realini, Tony

AU - Rhee, Douglas J.

AU - Schuman, Joel S.

AU - Singh, Kuldev

AU - Vollrath, Douglas

AU - Wollstein, Gadi

AU - Zack, Donald J.

AU - Allingham, R. Rand

AU - Pericak-Vance, Margaret A.

AU - Weinreb, Robert N.

AU - Zhang, Kang

AU - Hauser, Michael A.

AU - Richards, Julia E.

AU - Haines, Jonathan L.

AU - Wiggs, Janey L.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Purpose: 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. Design: 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). Conclusion: 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.

AB - Purpose: 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. Design: 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). Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=84872319362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872319362&partnerID=8YFLogxK

U2 - 10.1016/j.ajo.2012.07.023

DO - 10.1016/j.ajo.2012.07.023

M3 - Article

C2 - 23111177

AN - SCOPUS:84872319362

VL - 155

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

SN - 0002-9394

IS - 2

ER -