Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma

J. H. Kang, S. J. Loomis, B. L. Yaspan, J. C. Bailey, R. N. Weinreb, R. K. Lee, P. R. Lichter, D. L. Budenz, Yutao Liu, T. Realini, D. Gaasterland, T. Gaasterland, D. S. Friedman, C. A. Mccarty, S. E. Moroi, L. Olson, J. S. Schuman, K. Singh, D. Vollrath, G. Wollstein & 16 others D. J. Zack, M. Brilliant, A. J. Sit, W. G. Christen, J. Fingert, J. P. Forman, E. S. Buys, P. Kraft, K. Zhang, R. R. Allingham, M. A. Pericak-Vance, J. E. Richards, M. A. Hauser, J. L. Haines, J. L. Wiggs, L. R. Pasquale

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

AimsVascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.MethodsWe used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.ResultsThe vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.DiscussionAlthough the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Original languageEnglish (US)
Pages (from-to)662-671
Number of pages10
JournalEye (Basingstoke)
Volume28
Issue number6
DOIs
StatePublished - Jan 1 2014

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Blood Vessels
Genes
Glaucoma
Single Nucleotide Polymorphism
National Eye Institute (U.S.)
Encyclopedias
Primary Open Angle Glaucoma
Nitric Oxide Synthase Type III
Medical Genetics
Random Allocation
Visual Fields
Software
Perfusion
Genotype
Genome

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Kang, J. H., Loomis, S. J., Yaspan, B. L., Bailey, J. C., Weinreb, R. N., Lee, R. K., ... Pasquale, L. R. (2014). Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Basingstoke), 28(6), 662-671. https://doi.org/10.1038/eye.2014.42

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. / Kang, J. H.; Loomis, S. J.; Yaspan, B. L.; Bailey, J. C.; Weinreb, R. N.; Lee, R. K.; Lichter, P. R.; Budenz, D. L.; Liu, Yutao; Realini, T.; Gaasterland, D.; Gaasterland, T.; Friedman, D. S.; Mccarty, C. A.; Moroi, S. E.; Olson, L.; Schuman, J. S.; Singh, K.; Vollrath, D.; Wollstein, G.; Zack, D. J.; Brilliant, M.; Sit, A. J.; Christen, W. G.; Fingert, J.; Forman, J. P.; Buys, E. S.; Kraft, P.; Zhang, K.; Allingham, R. R.; Pericak-Vance, M. A.; Richards, J. E.; Hauser, M. A.; Haines, J. L.; Wiggs, J. L.; Pasquale, L. R.

In: Eye (Basingstoke), Vol. 28, No. 6, 01.01.2014, p. 662-671.

Research output: Contribution to journalArticle

Kang, JH, Loomis, SJ, Yaspan, BL, Bailey, JC, Weinreb, RN, Lee, RK, Lichter, PR, Budenz, DL, Liu, Y, Realini, T, Gaasterland, D, Gaasterland, 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, Forman, JP, Buys, ES, Kraft, P, Zhang, K, Allingham, RR, Pericak-Vance, MA, Richards, JE, Hauser, MA, Haines, JL, Wiggs, JL & Pasquale, LR 2014, 'Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma', Eye (Basingstoke), vol. 28, no. 6, pp. 662-671. https://doi.org/10.1038/eye.2014.42
Kang JH, Loomis SJ, Yaspan BL, Bailey JC, Weinreb RN, Lee RK et al. Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Basingstoke). 2014 Jan 1;28(6):662-671. https://doi.org/10.1038/eye.2014.42
Kang, J. H. ; Loomis, S. J. ; Yaspan, B. L. ; Bailey, J. C. ; Weinreb, R. N. ; Lee, R. K. ; Lichter, P. R. ; Budenz, D. L. ; Liu, Yutao ; Realini, T. ; Gaasterland, D. ; Gaasterland, T. ; Friedman, D. S. ; Mccarty, C. A. ; Moroi, S. E. ; Olson, L. ; Schuman, J. S. ; Singh, K. ; Vollrath, D. ; Wollstein, G. ; Zack, D. J. ; Brilliant, M. ; Sit, A. J. ; Christen, W. G. ; Fingert, J. ; Forman, J. P. ; Buys, E. S. ; Kraft, P. ; Zhang, K. ; Allingham, R. R. ; Pericak-Vance, M. A. ; Richards, J. E. ; Hauser, M. A. ; Haines, J. L. ; Wiggs, J. L. ; Pasquale, L. R. / Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. In: Eye (Basingstoke). 2014 ; Vol. 28, No. 6. pp. 662-671.
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title = "Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma",
abstract = "AimsVascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.MethodsWe used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.ResultsThe vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.DiscussionAlthough the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.",
author = "Kang, {J. H.} and Loomis, {S. J.} and Yaspan, {B. L.} and Bailey, {J. C.} and Weinreb, {R. N.} and Lee, {R. K.} and Lichter, {P. R.} and Budenz, {D. L.} and Yutao Liu and T. Realini and D. Gaasterland and T. Gaasterland and Friedman, {D. S.} and Mccarty, {C. A.} and Moroi, {S. E.} and L. Olson and Schuman, {J. S.} and K. Singh and D. Vollrath and G. Wollstein and Zack, {D. J.} and M. Brilliant and Sit, {A. J.} and Christen, {W. G.} and J. Fingert and Forman, {J. P.} and Buys, {E. S.} and P. Kraft and K. Zhang and Allingham, {R. R.} and Pericak-Vance, {M. A.} and Richards, {J. E.} and Hauser, {M. A.} and Haines, {J. L.} and Wiggs, {J. L.} and Pasquale, {L. R.}",
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T1 - Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma

AU - Kang, J. H.

AU - Loomis, S. J.

AU - Yaspan, B. L.

AU - Bailey, J. C.

AU - Weinreb, R. N.

AU - Lee, R. K.

AU - Lichter, P. R.

AU - Budenz, D. L.

AU - Liu, Yutao

AU - Realini, T.

AU - Gaasterland, D.

AU - Gaasterland, T.

AU - Friedman, D. S.

AU - Mccarty, C. A.

AU - Moroi, S. E.

AU - Olson, L.

AU - Schuman, J. S.

AU - Singh, K.

AU - Vollrath, D.

AU - Wollstein, G.

AU - Zack, D. J.

AU - Brilliant, M.

AU - Sit, A. J.

AU - Christen, W. G.

AU - Fingert, J.

AU - Forman, J. P.

AU - Buys, E. S.

AU - Kraft, P.

AU - Zhang, K.

AU - Allingham, R. R.

AU - Pericak-Vance, M. A.

AU - Richards, J. E.

AU - Hauser, M. A.

AU - Haines, J. L.

AU - Wiggs, J. L.

AU - Pasquale, L. R.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - AimsVascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.MethodsWe used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.ResultsThe vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.DiscussionAlthough the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

AB - AimsVascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.MethodsWe used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.ResultsThe vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.DiscussionAlthough the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

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