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Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
Kathryn P. Burdon,Stuart MacGregor,Alex W. Hewitt,Shiwani Sharma,Glyn Chidlow,Richard A. Mills,Patrick Danoy,Robert J Casson,Ananth C. Viswanathan,Jimmy Z. Liu,John Landers,Anjali K. Henders,John P. M. Wood,Emmanuelle Souzeau,April Crawford,Paul Leo,Jie Jin Wang,Elena Rochtchina,Dale R. Nyholt,Nicholas G. Martin,Grant W. Montgomery,Paul Mitchell,Brown,David A. Mackey,Jamie E Craig +24 more
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TLDR
This paper reported a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls.Abstract:
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.read more
Citations
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Journal ArticleDOI
Primary open-angle glaucoma.
Robert N. Weinreb,Christopher Kai-Shun Leung,Jonathan G Crowston,Felipe A. Medeiros,David S. Friedman,Janey L. Wiggs,Keith R Martin +6 more
TL;DR: Primary open-angle glaucoma (POAG) is the most common type and management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development.
Journal ArticleDOI
Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration
Gabriel Cuellar-Partida,Jamie E Craig,Kathryn P. Burdon,Jie Jin Wang,Brendan J Vote,Emmanuelle Souzeau,Ian L. McAllister,Timothy Isaacs,Stewart Lake,David A. Mackey,David A. Mackey,Ian J. Constable,Paul Mitchell,Alex W. Hewitt,Alex W. Hewitt,Stuart MacGregor +15 more
TL;DR: The genetic architecture of POAG and AMD is investigated using genome-wide array data and it is found that the genetic correlation between sexes for POAG was likely to be less than 1, suggesting that differences of prevalence among genders may be partly due to heritable factors.
Journal ArticleDOI
Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma
TL;DR: Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy and future therapeutic opportunities are highlighted.
Journal ArticleDOI
Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B.
Ada Congrains,Kei Kamide,Ryousuke Oguro,Osamu Yasuda,Keishi Miyata,Eiichiro Yamamoto,Tatsuo Kawai,Hiroshi Kusunoki,Hiroko Yamamoto,Yasushi Takeya,Koichi Yamamoto,Miyuki Onishi,Ken Sugimoto,Tomohiro Katsuya,Nobuhisa Awata,Kazunori Ikebe,Yasuyuki Gondo,Yuichi Oike,Mitsuru Ohishi,Hiromi Rakugi +19 more
TL;DR: It is suggested that several CVD-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation.
Journal ArticleDOI
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
Yi Lu,Veronique Vitart,Kathryn P. Burdon,Chiea Chuen Khor,Yelena Bykhovskaya,Alireza Mirshahi,Alex W. Hewitt,Alex W. Hewitt,Demelza Koehn,Pirro G. Hysi,Wishal D. Ramdas,Tanja Zeller,Eranga N. Vithana,Belinda K. Cornes,Wan Ting Tay,E. Shyong Tai,Ching-Yu Cheng,Jianjun Liu,Jianjun Liu,Jia Nee Foo,Seang-Mei Saw,Gudmar Thorleifsson,Kari Stefansson,Kari Stefansson,David P. Dimasi,Richard A. Mills,Jenny Mountain,Wei Ang,René Hoehn,Virginie J. M. Verhoeven,Franz H. Grus,Roger C. W. Wolfs,Raphaële Castagné,Karl J. Lackner,Henriët Springelkamp,Jian Yang,Fridbert Jonasson,Dexter Y L Leung,Li J. Chen,Clement C Y Tham,Igor Rudan,Igor Rudan,Zoran Vatavuk,Caroline Hayward,Jane Gibson,Angela J. Cree,Alex MacLeod,Sarah Ennis,Ozren Polasek,Harry Campbell,James F. Wilson,Ananth C. Viswanathan,Brian W Fleck,Xiaohui Li,David S. Siscovick,Kent D. Taylor,Jerome I. Rotter,Seyhan Yazar,Megan Ulmer,Jun Li,Brian L. Yaspan,Ayse Bilge Ozel,Julia E. Richards,Sayoko E. Moroi,Jonathan L. Haines,Jae H. Kang,Louis R. Pasquale,Louis R. Pasquale,R. Rand Allingham,Allison E. Ashley-Koch,Paul Mitchell,Jie Jin Wang,Alan F. Wright,Craig E. Pennell,Tim D. Spector,Terri L. Young,Terri L. Young,Caroline C W Klaver,Nicholas G. Martin,Grant W. Montgomery,Michael G. Anderson,Tin Aung,Colin E. Willoughby,Janey L. Wiggs,Chi P. Pang,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Andrew J. Lotery,Christopher J Hammond,Cornelia M. van Duijn,Michael A. Hauser,Yaron S. Rabinowitz,Norbert Pfeiffer,David A. Mackey,David A. Mackey,Jamie E Craig,Stuart MacGregor,Tien Yin Wong,Tien Yin Wong +98 more
TL;DR: A meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance showed that 2 CCT-associated loci conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls.
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