Common genetic determinants of intraocular pressure and primary open-angle glaucoma.
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 independen...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3342933?pdf=render |
| _version_ | 1818988511128190976 |
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| author | 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 DCCT/EDIC Research Group 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 Wellcome Trust Case Control Consortium 2 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 |
| author_facet | 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 DCCT/EDIC Research Group 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 Wellcome Trust Case Control Consortium 2 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 |
| author_sort | Leonieke M E van Koolwijk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T19:23:44Z |
| format | Article |
| id | doaj.art-2c3a0536b8874168b6cf89e7e4f94eda |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T19:23:44Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-2c3a0536b8874168b6cf89e7e4f94eda2022-12-21T19:28:55ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0185e100261110.1371/journal.pgen.1002611Common genetic determinants of intraocular pressure and primary open-angle glaucoma.Leonieke M E van KoolwijkWishal D RamdasM Kamran IkramNomdo M JansoniusFrancesca PasuttoPirro G HysiStuart MacgregorSarah F JanssenAlex W HewittAnanth C ViswanathanJacoline B ten BrinkS Mohsen HosseiniNajaf AminDominiek D G DesprietJacqueline J M Willemse-AssinkRogier KramerFernando RivadeneiraMaksim StruchalinYurii S AulchenkoNicole WeisschuhMatthias ZenkelChristian Y MardinEugen GramerUlrich Welge-LüssenGrant W MontgomeryFrancis CarbonaroTerri L YoungDCCT/EDIC Research GroupCéline BellenguezPeter McGuffinPaul J FosterFotis TopouzisPaul MitchellJie Jin WangTien Y WongMonika A CzudowskaAlbert HofmanAndre G UitterlindenRoger C W WolfsPaulus T V M de JongBen A OostraAndrew D PatersonWellcome Trust Case Control Consortium 2David A MackeyArthur A B BergenAndré ReisChristopher J HammondJohannes R VingerlingHans G LemijCaroline C W KlaverCornelia M van DuijnIntraocular 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.http://europepmc.org/articles/PMC3342933?pdf=render |
| spellingShingle | 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 DCCT/EDIC Research Group 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 Wellcome Trust Case Control Consortium 2 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 Common genetic determinants of intraocular pressure and primary open-angle glaucoma. PLoS Genetics |
| title | Common genetic determinants of intraocular pressure and primary open-angle glaucoma. |
| title_full | Common genetic determinants of intraocular pressure and primary open-angle glaucoma. |
| title_fullStr | Common genetic determinants of intraocular pressure and primary open-angle glaucoma. |
| title_full_unstemmed | Common genetic determinants of intraocular pressure and primary open-angle glaucoma. |
| title_short | Common genetic determinants of intraocular pressure and primary open-angle glaucoma. |
| title_sort | common genetic determinants of intraocular pressure and primary open angle glaucoma |
| url | http://europepmc.org/articles/PMC3342933?pdf=render |
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