Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia

Megan Ulmer, Jun Li, Brian L. Yaspan, Ayse Bilge Ozel, Julia E. Richards, Sayoko E. Moroi, Felicia Hawthorne, Donald L. Budenz, David S. Friedman, Douglas Gaasterland, Jonathan Haines, Jae H. Kang, Richard K Lee, Paul Lichter, Yutao Liu, Louis R. Pasquale, Margaret A Pericak-Vance, Anthony Realini, Joel S. Schuman, Kuldev SinghDouglas Vollrath, Robert Weinreb, Gadi Wollstein, Donald J. Zack, Kang Zhang, Terri Young, R. Rand Allingham, Janey L. Wiggs, Allison Ashley-Koch, Michael A. Hauser

Research output: Contribution to journalArticle

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Abstract

Purpose. To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. Methods. A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. Results. Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; β = -5.08 μm/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. Conclusions. The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.

Original languageEnglish
Pages (from-to)4468-4474
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number8
DOIs
StatePublished - Jul 1 2012

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Medical Genetics
Glaucoma
Single Nucleotide Polymorphism
Genome
Genes
Genome-Wide Association Study
Primary Open Angle Glaucoma
National Eye Institute (U.S.)
Odds Ratio
Cell Adhesion Molecules
Genetic Association Studies
Gene Library
Alleles

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia. / Ulmer, Megan; Li, Jun; Yaspan, Brian L.; Ozel, Ayse Bilge; Richards, Julia E.; Moroi, Sayoko E.; Hawthorne, Felicia; Budenz, Donald L.; Friedman, David S.; Gaasterland, Douglas; Haines, Jonathan; Kang, Jae H.; Lee, Richard K; Lichter, Paul; Liu, Yutao; Pasquale, Louis R.; Pericak-Vance, Margaret A; Realini, Anthony; Schuman, Joel S.; Singh, Kuldev; Vollrath, Douglas; Weinreb, Robert; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Young, Terri; Rand Allingham, R.; Wiggs, Janey L.; Ashley-Koch, Allison; Hauser, Michael A.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 8, 01.07.2012, p. 4468-4474.

Research output: Contribution to journalArticle

Ulmer, M, Li, J, Yaspan, BL, Ozel, AB, Richards, JE, Moroi, SE, Hawthorne, F, Budenz, DL, Friedman, DS, Gaasterland, D, Haines, J, Kang, JH, Lee, RK, Lichter, P, Liu, Y, Pasquale, LR, Pericak-Vance, MA, Realini, A, Schuman, JS, Singh, K, Vollrath, D, Weinreb, R, Wollstein, G, Zack, DJ, Zhang, K, Young, T, Rand Allingham, R, Wiggs, JL, Ashley-Koch, A & Hauser, MA 2012, 'Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia', Investigative Ophthalmology and Visual Science, vol. 53, no. 8, pp. 4468-4474. https://doi.org/10.1167/iovs.12-9784
Ulmer, Megan ; Li, Jun ; Yaspan, Brian L. ; Ozel, Ayse Bilge ; Richards, Julia E. ; Moroi, Sayoko E. ; Hawthorne, Felicia ; Budenz, Donald L. ; Friedman, David S. ; Gaasterland, Douglas ; Haines, Jonathan ; Kang, Jae H. ; Lee, Richard K ; Lichter, Paul ; Liu, Yutao ; Pasquale, Louis R. ; Pericak-Vance, Margaret A ; Realini, Anthony ; Schuman, Joel S. ; Singh, Kuldev ; Vollrath, Douglas ; Weinreb, Robert ; Wollstein, Gadi ; Zack, Donald J. ; Zhang, Kang ; Young, Terri ; Rand Allingham, R. ; Wiggs, Janey L. ; Ashley-Koch, Allison ; Hauser, Michael A. / Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 8. pp. 4468-4474.
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abstract = "Purpose. To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. Methods. A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. Results. Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; β = -5.08 μm/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. Conclusions. The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.",
author = "Megan Ulmer and Jun Li and Yaspan, {Brian L.} and Ozel, {Ayse Bilge} and Richards, {Julia E.} and Moroi, {Sayoko E.} and Felicia Hawthorne and Budenz, {Donald L.} and Friedman, {David S.} and Douglas Gaasterland and Jonathan Haines and Kang, {Jae H.} and Lee, {Richard K} and Paul Lichter and Yutao Liu and Pasquale, {Louis R.} and Pericak-Vance, {Margaret A} and Anthony Realini and Schuman, {Joel S.} and Kuldev Singh and Douglas Vollrath and Robert Weinreb and Gadi Wollstein and Zack, {Donald J.} and Kang Zhang and Terri Young and {Rand Allingham}, R. and Wiggs, {Janey L.} and Allison Ashley-Koch and Hauser, {Michael A.}",
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T1 - Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia

AU - Ulmer, Megan

AU - Li, Jun

AU - Yaspan, Brian L.

AU - Ozel, Ayse Bilge

AU - Richards, Julia E.

AU - Moroi, Sayoko E.

AU - Hawthorne, Felicia

AU - Budenz, Donald L.

AU - Friedman, David S.

AU - Gaasterland, Douglas

AU - Haines, Jonathan

AU - Kang, Jae H.

AU - Lee, Richard K

AU - Lichter, Paul

AU - Liu, Yutao

AU - Pasquale, Louis R.

AU - Pericak-Vance, Margaret A

AU - Realini, Anthony

AU - Schuman, Joel S.

AU - Singh, Kuldev

AU - Vollrath, Douglas

AU - Weinreb, Robert

AU - Wollstein, Gadi

AU - Zack, Donald J.

AU - Zhang, Kang

AU - Young, Terri

AU - Rand Allingham, R.

AU - Wiggs, Janey L.

AU - Ashley-Koch, Allison

AU - Hauser, Michael A.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Purpose. To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. Methods. A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. Results. Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; β = -5.08 μm/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. Conclusions. The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.

AB - Purpose. To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. Methods. A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. Results. Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; β = -5.08 μm/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. Conclusions. The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.

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