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Common genetic variants associated with open-angle glaucoma

Common genetic variants associated with open-angle glaucoma
Common genetic variants associated with open-angle glaucoma
Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.
2464-2471
Ramdas, Wishal D.
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van Koolwijk, Leonieke M.E.
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Lemij, Hans G.
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Pasutto, Francesca
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Cree, Angela J.
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Thorleifsson, Gudmar
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Janssen, Sarah F
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Jacoline, Ten Brink
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Amin, Najaf
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Rivadeneira, Fernando
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Wolfs, Roger C.W.
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Walters, G. Bragi
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Jonasson, Fridbert
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Weisschuh, Nicole
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Mardin, Christian Y.
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Gibson, Jane
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Zegers, Richard H.C.
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Hofman, Albert
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de Jong, Paulus T.V.M.
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Uitterlinden, André G.
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Oostra, Ben A.
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Thorsteinsdottir, Unnur
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Gramer, Eugen
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Welgen-Lüssen, Ulrich C.
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Kirwan, James F.
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Bergen, Arthur A.B.
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Reis, André
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Stefansson, Kari
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Lotery, Andrew J.
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Vingerling, Johannes R.
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Jansonius, Nomdo M.
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Klaver, Caroline C.W.
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van Duijn, Cornelia M.
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Ramdas, Wishal D.
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van Koolwijk, Leonieke M.E.
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Lemij, Hans G.
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Pasutto, Francesca
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Cree, Angela J.
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Thorleifsson, Gudmar
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Janssen, Sarah F
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Jacoline, Ten Brink
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Amin, Najaf
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Rivadeneira, Fernando
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Wolfs, Roger C.W.
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Walters, G. Bragi
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Weisschuh, Nicole
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Mardin, Christian Y.
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Gibson, Jane
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Zegers, Richard H.C.
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Hofman, Albert
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de Jong, Paulus T.V.M.
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Uitterlinden, André G.
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Oostra, Ben A.
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Thorsteinsdottir, Unnur
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Gramer, Eugen
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Welgen-Lüssen, Ulrich C.
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Kirwan, James F.
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Bergen, Arthur A.B.
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Reis, André
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Stefansson, Kari
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Lotery, Andrew J.
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Vingerling, Johannes R.
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Jansonius, Nomdo M.
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Klaver, Caroline C.W.
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van Duijn, Cornelia M.
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Ramdas, Wishal D., van Koolwijk, Leonieke M.E., Lemij, Hans G., Pasutto, Francesca, Cree, Angela J., Thorleifsson, Gudmar, Janssen, Sarah F, Jacoline, Ten Brink, Amin, Najaf, Rivadeneira, Fernando, Wolfs, Roger C.W., Walters, G. Bragi, Jonasson, Fridbert, Weisschuh, Nicole, Mardin, Christian Y., Gibson, Jane, Zegers, Richard H.C., Hofman, Albert, de Jong, Paulus T.V.M., Uitterlinden, André G., Oostra, Ben A., Thorsteinsdottir, Unnur, Gramer, Eugen, Welgen-Lüssen, Ulrich C., Kirwan, James F., Bergen, Arthur A.B., Reis, André, Stefansson, Kari, Lotery, Andrew J., Vingerling, Johannes R., Jansonius, Nomdo M., Klaver, Caroline C.W. and van Duijn, Cornelia M. (2011) Common genetic variants associated with open-angle glaucoma. Human Molecular Genetics, 20 (12), 2464-2471. (doi:10.1093/hmg/ddr120). (PMID:21427129)

Record type: Article

Abstract

Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.

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More information

e-pub ahead of print date: 22 March 2011
Published date: 15 June 2011
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 338863
URI: http://eprints.soton.ac.uk/id/eprint/338863
PURE UUID: d6c67bb9-dd3e-47c6-a5ad-a305a1fa9431
ORCID for Angela J. Cree: ORCID iD orcid.org/0000-0002-1987-8900
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 17 May 2012 16:02
Last modified: 15 Mar 2024 03:24

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Contributors

Author: Wishal D. Ramdas
Author: Leonieke M.E. van Koolwijk
Author: Hans G. Lemij
Author: Francesca Pasutto
Author: Angela J. Cree ORCID iD
Author: Gudmar Thorleifsson
Author: Sarah F Janssen
Author: Ten Brink Jacoline
Author: Najaf Amin
Author: Fernando Rivadeneira
Author: Roger C.W. Wolfs
Author: G. Bragi Walters
Author: Fridbert Jonasson
Author: Nicole Weisschuh
Author: Christian Y. Mardin
Author: Jane Gibson ORCID iD
Author: Richard H.C. Zegers
Author: Albert Hofman
Author: Paulus T.V.M. de Jong
Author: André G. Uitterlinden
Author: Ben A. Oostra
Author: Unnur Thorsteinsdottir
Author: Eugen Gramer
Author: Ulrich C. Welgen-Lüssen
Author: James F. Kirwan
Author: Arthur A.B. Bergen
Author: André Reis
Author: Kari Stefansson
Author: Johannes R. Vingerling
Author: Nomdo M. Jansonius
Author: Caroline C.W. Klaver
Author: Cornelia M. van Duijn

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