Common genetic determinants of intraocular pressure and primary open-angle glaucoma

Leonieke M E van Koolwijk; Wishal D Ramdas; M Kamran Ikram; Nomdo M Jansonius; Francesca Pasutto; Pirro G Hysi; Stuart Macgregor; Sarah F Janssen; Alex W Hewitt; Ananth C Viswanathan; Jacoline B ten Brink; S Mohsen Hosseini; Najaf Amin; Dominiek D G Despriet; Jacqueline J M Willemse-Assink; Rogier Kramer; Fernando Rivadeneira; Maksim Struchalin; Yurii S Aulchenko; Nicole Weisschuh; Matthias Zenkel; Christian Y Mardin; Eugen Gramer; Ulrich Welge-Lüssen; Grant W Montgomery; Francis Carbonaro; Terri L Young; Céline Bellenguez; Peter McGuffin; Paul J Foster; Fotis Topouzis; Paul Mitchell; Jie Jin Wang; Tien Y Wong; Monika A Czudowska; Albert Hofman; Andre G Uitterlinden; Roger C W Wolfs; Paulus T V M de Jong; Ben A Oostra; Andrew D Paterson; David A Mackey; Arthur A B Bergen; André Reis; Christopher J Hammond; Johannes R Vingerling; Hans G Lemij; Caroline C W Klaver; Cornelia M van Duijn

doi:10.1371/journal.pgen.1002611

Common genetic determinants of intraocular pressure and primary open-angle glaucoma

Leonieke M E van Koolwijk, Wishal D Ramdas, M Kamran Ikram, Nomdo M Jansonius, Francesca Pasutto, Pirro G Hysi, Stuart Macgregor, Sarah F Janssen, Alex W Hewitt, Ananth C Viswanathan, Jacoline B ten Brink, S Mohsen Hosseini, Najaf Amin, Dominiek D G Despriet, Jacqueline J M Willemse-Assink, Rogier Kramer, Fernando Rivadeneira, Maksim Struchalin, Yurii S Aulchenko, Nicole WeisschuhMatthias Zenkel, Christian Y Mardin, Eugen Gramer, Ulrich Welge-Lüssen, Grant W Montgomery, Francis Carbonaro, Terri L Young, , Céline Bellenguez, Peter McGuffin, Paul J Foster, Fotis Topouzis, Paul Mitchell, Jie Jin Wang, Tien Y Wong, Monika A Czudowska, Albert Hofman, Andre G Uitterlinden, Roger C W Wolfs, Paulus T V M de Jong, Ben A Oostra, Andrew D Paterson, David A Mackey, Arthur A B Bergen, André Reis, Christopher J Hammond, Johannes R Vingerling, Hans G Lemij, Caroline C W Klaver, Cornelia M van Duijn

Glaucoma

Research output: Contribution to journal › Article › Research › peer-review

Abstract

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

Original language	English
Pages (from-to)	e1002611
Journal	PLoS Genetics
Volume	8
Issue number	5
DOIs	https://doi.org/10.1371/journal.pgen.1002611
Publication status	Published - 2012

Keywords

Aged
Aged, 80 and over
Case-Control Studies
Ciliary Body/metabolism
Female
Genome-Wide Association Study
Glaucoma, Open-Angle/genetics
Humans
Intraocular Pressure/genetics
Male
Middle Aged
Nerve Tissue Proteins/genetics
Optic Nerve/metabolism
Polymorphism, Single Nucleotide
Trabecular Meshwork/metabolism

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10.1371/journal.pgen.1002611

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van Koolwijk, L. M. E., Ramdas, W. D., Ikram, M. K., Jansonius, N. M., Pasutto, F., Hysi, P. G., Macgregor, S., Janssen, S. F., Hewitt, A. W., Viswanathan, A. C., ten Brink, J. B., Hosseini, S. M., Amin, N., Despriet, D. D. G., Willemse-Assink, J. J. M., Kramer, R., Rivadeneira, F., Struchalin, M., Aulchenko, Y. S., ... van Duijn, C. M. (2012). Common genetic determinants of intraocular pressure and primary open-angle glaucoma. PLoS Genetics, 8(5), e1002611. https://doi.org/10.1371/journal.pgen.1002611

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title = "Common genetic determinants of intraocular pressure and primary open-angle glaucoma",

abstract = "Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.",

keywords = "Aged, Aged, 80 and over, Case-Control Studies, Ciliary Body/metabolism, Female, Genome-Wide Association Study, Glaucoma, Open-Angle/genetics, Humans, Intraocular Pressure/genetics, Male, Middle Aged, Nerve Tissue Proteins/genetics, Optic Nerve/metabolism, Polymorphism, Single Nucleotide, Trabecular Meshwork/metabolism",

author = "{van Koolwijk}, {Leonieke M E} and Ramdas, {Wishal D} and Ikram, {M Kamran} and Jansonius, {Nomdo M} and Francesca Pasutto and Hysi, {Pirro G} and Stuart Macgregor and Janssen, {Sarah F} and Hewitt, {Alex W} and Viswanathan, {Ananth C} and {ten Brink}, {Jacoline B} and Hosseini, {S Mohsen} and Najaf Amin and Despriet, {Dominiek D G} and Willemse-Assink, {Jacqueline J M} and Rogier Kramer and Fernando Rivadeneira and Maksim Struchalin and Aulchenko, {Yurii S} and Nicole Weisschuh and Matthias Zenkel and Mardin, {Christian Y} and Eugen Gramer and Ulrich Welge-L{\"u}ssen and Montgomery, {Grant W} and Francis Carbonaro and Young, {Terri L} and C{\'e}line Bellenguez and Peter McGuffin and Foster, {Paul J} and Fotis Topouzis and Paul Mitchell and Wang, {Jie Jin} and Wong, {Tien Y} and Czudowska, {Monika A} and Albert Hofman and Uitterlinden, {Andre G} and Wolfs, {Roger C W} and {de Jong}, {Paulus T V M} and Oostra, {Ben A} and Paterson, {Andrew D} and Mackey, {David A} and Bergen, {Arthur A B} and Andr{\'e} Reis and Hammond, {Christopher J} and Vingerling, {Johannes R} and Lemij, {Hans G} and Klaver, {Caroline C W} and {van Duijn}, {Cornelia M}",

year = "2012",

doi = "10.1371/journal.pgen.1002611",

language = "English",

volume = "8",

pages = "e1002611",

number = "5",

}

van Koolwijk, LME, Ramdas, WD, Ikram, MK, Jansonius, NM, Pasutto, F, Hysi, PG, Macgregor, S, Janssen, SF, Hewitt, AW, Viswanathan, AC, ten Brink, JB, Hosseini, SM, Amin, N, Despriet, DDG, Willemse-Assink, JJM, Kramer, R, Rivadeneira, F, Struchalin, M, Aulchenko, YS, Weisschuh, N, Zenkel, M, Mardin, CY, Gramer, E, Welge-Lüssen, U, Montgomery, GW, Carbonaro, F, Young, TL, Bellenguez, C, McGuffin, P, Foster, PJ, Topouzis, F, Mitchell, P, Wang, JJ, Wong, TY, Czudowska, MA, Hofman, A, Uitterlinden, AG, Wolfs, RCW, de Jong, PTVM, Oostra, BA, Paterson, AD, Mackey, DA, Bergen, AAB, Reis, A, Hammond, CJ, Vingerling, JR, Lemij, HG & Klaver, CCW & van Duijn, CM 2012, 'Common genetic determinants of intraocular pressure and primary open-angle glaucoma', PLoS Genetics, vol. 8, no. 5, pp. e1002611. https://doi.org/10.1371/journal.pgen.1002611

TY - JOUR

T1 - Common genetic determinants of intraocular pressure and primary open-angle glaucoma

AU - van Koolwijk, Leonieke M E

AU - Ramdas, Wishal D

AU - Ikram, M Kamran

AU - Jansonius, Nomdo M

AU - Pasutto, Francesca

AU - Hysi, Pirro G

AU - Macgregor, Stuart

AU - Janssen, Sarah F

AU - Hewitt, Alex W

AU - Viswanathan, Ananth C

AU - ten Brink, Jacoline B

AU - Hosseini, S Mohsen

AU - Amin, Najaf

AU - Despriet, Dominiek D G

AU - Willemse-Assink, Jacqueline J M

AU - Kramer, Rogier

AU - Rivadeneira, Fernando

AU - Struchalin, Maksim

AU - Aulchenko, Yurii S

AU - Weisschuh, Nicole

AU - Zenkel, Matthias

AU - Mardin, Christian Y

AU - Gramer, Eugen

AU - Welge-Lüssen, Ulrich

AU - Montgomery, Grant W

AU - Carbonaro, Francis

AU - Young, Terri L

AU - Bellenguez, Céline

AU - McGuffin, Peter

AU - Foster, Paul J

AU - Topouzis, Fotis

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Wong, Tien Y

AU - Czudowska, Monika A

AU - Hofman, Albert

AU - Uitterlinden, Andre G

AU - Wolfs, Roger C W

AU - de Jong, Paulus T V M

AU - Oostra, Ben A

AU - Paterson, Andrew D

AU - Mackey, David A

AU - Bergen, Arthur A B

AU - Reis, André

AU - Hammond, Christopher J

AU - Vingerling, Johannes R

AU - Lemij, Hans G

AU - Klaver, Caroline C W

AU - van Duijn, Cornelia M

PY - 2012

Y1 - 2012

N2 - Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

AB - Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Ciliary Body/metabolism

KW - Female

KW - Genome-Wide Association Study

KW - Glaucoma, Open-Angle/genetics

KW - Humans

KW - Intraocular Pressure/genetics

KW - Male

KW - Middle Aged

KW - Nerve Tissue Proteins/genetics

KW - Optic Nerve/metabolism

KW - Polymorphism, Single Nucleotide

KW - Trabecular Meshwork/metabolism

U2 - 10.1371/journal.pgen.1002611

DO - 10.1371/journal.pgen.1002611

M3 - Article

C2 - 22570627

SN - 1553-7390

VL - 8

SP - e1002611

JO - PLoS Genetics

JF - PLoS Genetics

IS - 5

ER -

Common genetic determinants of intraocular pressure and primary open-angle glaucoma

Abstract

Keywords

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