Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss

Stephanie J. Loomis, Jae H. Kang, Robert N. Weinreb, Brian L. Yaspan, Jessica N. Cooke Bailey, Douglas Gaasterland, Terry Gaasterland, Richard K. Lee, Paul R. Lichter, Donald L. Budenz, Yutao Liu, Tony Realini, David S. Friedman, Catherine A. McCarty, Sayoko E. Moroi, Lana Olson, Joel S. Schuman, Kuldev Singh, Douglas Vollrath, Gadi Wollstein & 14 others Donald J. Zack, Murray Brilliant, Arthur J. Sit, William G. Christen, John Fingert, Peter Kraft, Kang Zhang, R. Rand Allingham, Margaret A. Pericak-Vance, Julia E. Richards, Michael A. Hauser, Jonathan L. Haines, Louis R. Pasquale, Janey L. Wiggs

Research output: Contribution to journalArticle

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Abstract

Purpose The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Design Case-control study. Participants We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). Methods We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7×10-4 was used to account for multiple comparisons. Main Outcome Measures Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. Results We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61×10 -7). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59×10-5). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07×10-4), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. Conclusions CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.

Original languageEnglish (US)
Pages (from-to)508-516
Number of pages9
JournalOphthalmology
Volume121
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

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Caveolin 2
Caveolin 1
Visual Fields
Single Nucleotide Polymorphism
Glaucoma
National Eye Institute (U.S.)
Medical Genetics
Primary Open Angle Glaucoma
Logistic Models
HapMap Project
Caveolins
Genes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Loomis, S. J., Kang, J. H., Weinreb, R. N., Yaspan, B. L., Cooke Bailey, J. N., Gaasterland, D., ... Wiggs, J. L. (2014). Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology, 121(2), 508-516. https://doi.org/10.1016/j.ophtha.2013.09.012

Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. / Loomis, Stephanie J.; Kang, Jae H.; Weinreb, Robert N.; Yaspan, Brian L.; Cooke Bailey, Jessica N.; Gaasterland, Douglas; Gaasterland, Terry; Lee, Richard K.; Lichter, Paul R.; Budenz, Donald L.; Liu, Yutao; Realini, Tony; Friedman, David S.; McCarty, Catherine A.; Moroi, Sayoko E.; Olson, Lana; Schuman, Joel S.; Singh, Kuldev; Vollrath, Douglas; Wollstein, Gadi; Zack, Donald J.; Brilliant, Murray; Sit, Arthur J.; Christen, William G.; Fingert, John; Kraft, Peter; Zhang, Kang; Allingham, R. Rand; Pericak-Vance, Margaret A.; Richards, Julia E.; Hauser, Michael A.; Haines, Jonathan L.; Pasquale, Louis R.; Wiggs, Janey L.

In: Ophthalmology, Vol. 121, No. 2, 01.02.2014, p. 508-516.

Research output: Contribution to journalArticle

Loomis, SJ, Kang, JH, Weinreb, RN, Yaspan, BL, Cooke Bailey, JN, Gaasterland, D, Gaasterland, T, Lee, RK, Lichter, PR, Budenz, DL, Liu, Y, Realini, T, Friedman, DS, McCarty, CA, Moroi, SE, Olson, L, Schuman, JS, Singh, K, Vollrath, D, Wollstein, G, Zack, DJ, Brilliant, M, Sit, AJ, Christen, WG, Fingert, J, Kraft, P, Zhang, K, Allingham, RR, Pericak-Vance, MA, Richards, JE, Hauser, MA, Haines, JL, Pasquale, LR & Wiggs, JL 2014, 'Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss', Ophthalmology, vol. 121, no. 2, pp. 508-516. https://doi.org/10.1016/j.ophtha.2013.09.012
Loomis, Stephanie J. ; Kang, Jae H. ; Weinreb, Robert N. ; Yaspan, Brian L. ; Cooke Bailey, Jessica N. ; Gaasterland, Douglas ; Gaasterland, Terry ; Lee, Richard K. ; Lichter, Paul R. ; Budenz, Donald L. ; Liu, Yutao ; Realini, Tony ; Friedman, David S. ; McCarty, Catherine A. ; Moroi, Sayoko E. ; Olson, Lana ; Schuman, Joel S. ; Singh, Kuldev ; Vollrath, Douglas ; Wollstein, Gadi ; Zack, Donald J. ; Brilliant, Murray ; Sit, Arthur J. ; Christen, William G. ; Fingert, John ; Kraft, Peter ; Zhang, Kang ; Allingham, R. Rand ; Pericak-Vance, Margaret A. ; Richards, Julia E. ; Hauser, Michael A. ; Haines, Jonathan L. ; Pasquale, Louis R. ; Wiggs, Janey L. / Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. In: Ophthalmology. 2014 ; Vol. 121, No. 2. pp. 508-516.
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author = "Loomis, {Stephanie J.} and Kang, {Jae H.} and Weinreb, {Robert N.} and Yaspan, {Brian L.} and {Cooke Bailey}, {Jessica N.} and Douglas Gaasterland and Terry Gaasterland and Lee, {Richard K.} and Lichter, {Paul R.} and Budenz, {Donald L.} and Yutao Liu and Tony Realini and Friedman, {David S.} and McCarty, {Catherine A.} and Moroi, {Sayoko E.} and Lana Olson and Schuman, {Joel S.} and Kuldev Singh and Douglas Vollrath and Gadi Wollstein and Zack, {Donald J.} and Murray Brilliant and Sit, {Arthur J.} and Christen, {William G.} and John Fingert and Peter Kraft and Kang Zhang and Allingham, {R. Rand} and Pericak-Vance, {Margaret A.} and Richards, {Julia E.} and Hauser, {Michael A.} and Haines, {Jonathan L.} and Pasquale, {Louis R.} and Wiggs, {Janey L.}",
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TY - JOUR

T1 - Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss

AU - Loomis, Stephanie J.

AU - Kang, Jae H.

AU - Weinreb, Robert N.

AU - Yaspan, Brian L.

AU - Cooke Bailey, Jessica N.

AU - Gaasterland, Douglas

AU - Gaasterland, Terry

AU - Lee, Richard K.

AU - Lichter, Paul R.

AU - Budenz, Donald L.

AU - Liu, Yutao

AU - Realini, Tony

AU - Friedman, David S.

AU - McCarty, Catherine A.

AU - Moroi, Sayoko E.

AU - Olson, Lana

AU - Schuman, Joel S.

AU - Singh, Kuldev

AU - Vollrath, Douglas

AU - Wollstein, Gadi

AU - Zack, Donald J.

AU - Brilliant, Murray

AU - Sit, Arthur J.

AU - Christen, William G.

AU - Fingert, John

AU - Kraft, Peter

AU - Zhang, Kang

AU - Allingham, R. Rand

AU - Pericak-Vance, Margaret A.

AU - Richards, Julia E.

AU - Hauser, Michael A.

AU - Haines, Jonathan L.

AU - Pasquale, Louis R.

AU - Wiggs, Janey L.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Purpose The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Design Case-control study. Participants We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). Methods We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7×10-4 was used to account for multiple comparisons. Main Outcome Measures Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. Results We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61×10 -7). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59×10-5). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07×10-4), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. Conclusions CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.

AB - Purpose The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Design Case-control study. Participants We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). Methods We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7×10-4 was used to account for multiple comparisons. Main Outcome Measures Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. Results We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61×10 -7). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59×10-5). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07×10-4), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. Conclusions CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.

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