Genome-wide association analysis identifies TXNRD2 , ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma
Jessica N. Cooke Bailey,Stephanie Loomis,Jae H. Kang,R. Rand Allingham,Puya Gharahkhani,Chiea Chuen Khor,Chiea Chuen Khor,Kathryn P. Burdon,Kathryn P. Burdon,Hugues Aschard,Daniel I. Chasman,Robert P. Igo,Pirro G. Hysi,Craig A. Glastonbury,Allison E. Ashley-Koch,Murray H. Brilliant,Andrew A. Brown,Donald L. Budenz,Alfonso Buil,Ching-Yu Cheng,Ching-Yu Cheng,Hyon K. Choi,William G. Christen,Gary C. Curhan,Immaculata De Vivo,John H. Fingert,Paul J. Foster,Paul J. Foster,Charles S. Fuchs,Douglas E. Gaasterland,Terry Gaasterland,Alex W. Hewitt,Frank B. Hu,David J. Hunter,Anthony P Khawaja,Richard K. Lee,Zheng Li,Paul R. Lichter,David A. Mackey,David A. Mackey,Peter McGuffin,Paul Mitchell,Sayoko E. Moroi,Shamira A. Perera,Shamira A. Perera,Keating W. Pepper,Qibin Qi,Tony Realini,Julia E. Richards,Paul M. Ridker,Eric B. Rimm,Robert Ritch,Marylyn D. Ritchie,Joel S. Schuman,William K. Scott,Kuldev Singh,Arthur J. Sit,Yeunjoo E. Song,Rulla M. Tamimi,Fotis Topouzis,Ananth C. Viswanathan,Shefali S. Verma,Douglas Vollrath,Jie Jin Wang,Nicole Weisschuh,Bernd Wissinger,Gadi Wollstein,Tien Yin Wong,Tien Yin Wong,Brian L. Yaspan,Donald J. Zack,Kang Zhang,Robert N. Weinreb,Margaret A. Pericak-Vance,Kerrin S. Small,Christopher J Hammond,Tin Aung,Tin Aung,Yutao Liu,Eranga N. Vithana,Eranga N. Vithana,Stuart MacGregor,Jamie E Craig,Peter Kraft,Gareth R. Howell,Michael A. Hauser,Louis R. Pasquale,Jonathan L. Haines,Janey L. Wiggs +88 more
TLDR
New pathways underlying POAG susceptibility are identified and new targets for preventative therapies are suggested, including TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head.Abstract:
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.read more
Citations
More filters
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.
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
TL;DR: 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.
Journal ArticleDOI
Genetics of glaucoma.
TL;DR: Genetic and genomic studies are defining important biological pathways and processes that contribute to disease pathogenesis, including genome-wide association studies (GWAS) for common adult-onset glaucoma.
Journal ArticleDOI
Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.
Anthony P Khawaja,Anthony P Khawaja,Jessica N. Cooke Bailey,Nicholas J. Wareham,Robert A. Scott,Mark James Simcoe,Robert P. Igo,Yeunjoo E. Song,Robert Wojciechowski,Ching-Yu Cheng,Peng T. Khaw,Louis R. Pasquale,Jonathan L. Haines,Paul J. Foster,Janey L. Wiggs,Christopher J Hammond,Pirro G. Hysi,UK Biobank Eye +17 more
TL;DR: A meta-analysis of 139,555 Europeans identifies 68 new genomic loci associated with intraocular pressure, 68 of which are novel, which suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP.
Journal ArticleDOI
Genome-wide Association Study of Intraocular Pressure Uncovers New Pathways to Glaucoma
Stuart MacGregor,Jue-Sheng Ong,Jiyuan An,Xikun Han,Tiger Zhou,Owen M. Siggs,Matthew Law,Emmanuelle Souzeau,Shiwani Sharma,David J. Lynn,David J. Lynn,Jonathan Beesley,Bronwyn Sheldrick,Richard A. Mills,John Landers,Jonathan B Ruddle,Stuart L. Graham,Paul R. Healey,Andrew White,Robert J Casson,Stephen Best,John R. Grigg,Ivan Goldberg,Joseph E. Powell,Joseph E. Powell,David C. Whiteman,Graham L. Radford-Smith,Graham L. Radford-Smith,Nicholas G. Martin,Grant W. Montgomery,Kathryn P. Burdon,Kathryn P. Burdon,David A. Mackey,David A. Mackey,Puya Gharahkhani,Jamie E Craig,Alex W. Hewitt,Alex W. Hewitt +37 more
TL;DR: A combined analysis of participants from the UK Biobank and the International Glaucoma Genetic Consortium identifies 85 new loci for intraocular pressure (IOP), and pathway analysis uncovers new pathways associated with both IOP and glAUcoma.
References
More filters
Journal ArticleDOI
The Human Genome Browser at UCSC
W. James Kent,Charles W. Sugnet,Terrence S. Furey,Krishna M. Roskin,Tom H. Pringle,Alan M. Zahler,and David Haussler +6 more
TL;DR: A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu.
Journal ArticleDOI
Principal components analysis corrects for stratification in genome-wide association studies
Alkes L. Price,Alkes L. Price,Nick Patterson,Robert M. Plenge,Robert M. Plenge,Michael E. Weinblatt,Nancy A. Shadick,David Reich,David Reich +8 more
TL;DR: This work describes a method that enables explicit detection and correction of population stratification on a genome-wide scale and uses principal components analysis to explicitly model ancestry differences between cases and controls.
Journal ArticleDOI
The number of people with glaucoma worldwide in 2010 and 2020
Harry A. Quigley,Aimee T. Broman +1 more
TL;DR: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians, and it will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG.
Journal ArticleDOI
Number of people with glaucoma worldwide.
TL;DR: Improved methods of screening and therapy for glaucoma are urgently needed, as it is the second leading cause of vision loss in the world.
Journal ArticleDOI
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
Kristin G. Ardlie,David S. DeLuca,Ayellet V. Segrè,Timothy J. Sullivan,Taylor Young,Ellen Gelfand,Casandra A. Trowbridge,Julian Maller,Taru Tukiainen,Monkol Lek,Lucas D. Ward,Pouya Kheradpour,Benjamin Iriarte,Yan Meng,Cameron D. Palmer,Tõnu Esko,Wendy Winckler,Joel N. Hirschhorn,Manolis Kellis,Daniel G. MacArthur,Gad Getz,Andrey A. Shabalin,Gen Li,Yi-Hui Zhou,Andrew B. Nobel,Ivan Rusyn,Fred A. Wright,Tuuli Lappalainen,Pedro G. Ferreira,Halit Ongen,Manuel A. Rivas,Alexis Battle,Sara Mostafavi,Jean Monlong,Michael Sammeth,Marta Melé,Ferran Reverter,Jakob M. Goldmann,Daphne Koller,Roderic Guigó,Mark I. McCarthy,Emmanouil T. Dermitzakis,Eric R. Gamazon,Hae Kyung Im,Anuar Konkashbaev,Dan L. Nicolae,Nancy J. Cox,Timothée Flutre,Xiaoquan Wen,Matthew Stephens,Jonathan K. Pritchard,Zhidong Tu,Bin Zhang,Tao Huang,Quan Long,Luan Lin,Jialiang Yang,Jun Zhu,Jun Liu,Amanda Brown,Bernadette Mestichelli,Denee Tidwell,Edmund Lo,Mike Salvatore,Saboor Shad,Jeffrey A. Thomas,John T. Lonsdale,Michael T. Moser,Bryan Gillard,Ellen Karasik,Kimberly Ramsey,Christopher Choi,Barbara A. Foster,John Syron,Johnell Fleming,Harold Magazine,Rick Hasz,Gary Walters,Jason Bridge,Mark Miklos,Susan L. Sullivan,Laura Barker,Heather M. Traino,Maghboeba Mosavel,Laura A. Siminoff,Dana R. Valley,Daniel C. Rohrer,Scott D. Jewell,Philip A. Branton,Leslie H. Sobin,Mary Barcus,Liqun Qi,Jeffrey McLean,Pushpa Hariharan,Ki Sung Um,Shenpei Wu,David Tabor,Charles Shive,Anna M. Smith,Stephen A. Buia,Anita H. Undale,Karna Robinson,Nancy Roche,Kimberly M. Valentino,Angela Britton,Robin Burges,Debra Bradbury,Kenneth W. Hambright,John Seleski,Greg E. Korzeniewski,Kenyon Erickson,Yvonne Marcus,Jorge Tejada,Mehran Taherian,Chunrong Lu,Margaret J. Basile,Deborah C. Mash,Simona Volpi,Jeffery P. Struewing,Gary F. Temple,Joy T. Boyer,Deborah Colantuoni,Roger Little,Susan E. Koester,Latarsha J. Carithers,Helen M. Moore,Ping Guan,Carolyn C. Compton,Sherilyn Sawyer,Joanne P. Demchok,Jimmie B. Vaught,Chana A. Rabiner,Nicole C. Lockhart +132 more
TL;DR: The landscape of gene expression across tissues is described, thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants are cataloged, complex network relationships are described, and signals from genome-wide association studies explained by eQTLs are identified.
Related Papers (5)
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
Kathryn P. Burdon,Stuart MacGregor,Alex W. Hewitt,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,Jie Jin Wang,Elena Rochtchina,Dale R. Nyholt,Nicholas G. Martin,Grant W. Montgomery,Paul Mitchell,Matthew A. Brown,David A. Mackey,David A. Mackey,David A. Mackey,Jamie E Craig +28 more
Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma
Janey L. Wiggs,Brian L. Yaspan,Michael A. Hauser,Jae H. Kang,R. Rand Allingham,Lana M. Olson,Wael Abdrabou,Baojian Fan,Dan Y. Wang,Wendy Brodeur,Donald L. Budenz,Joseph Caprioli,Andrew Crenshaw,Kristy Crooks,E. DelBono,Kimberly F. Doheny,David S. Friedman,Douglas E. Gaasterland,Terry Gaasterland,Cathy C. Laurie,Richard K. Lee,Paul R. Lichter,Stephanie Loomis,Yutao Liu,Felipe A. Medeiros,Catherine A. McCarty,Daniel B. Mirel,Sayoko E. Moroi,David C. Musch,Anthony Realini,Frank W. Rozsa,Joel S. Schuman,Kathleen M. Scott,Kuldev Singh,Joshua D. Stein,Edward H. Trager,Paul C. VanVeldhuisen,Douglas Vollrath,Gadi Wollstein,Sachiko Yoneyama,Kang Zhang,Robert N. Weinreb,Jason Ernst,Manolis Kellis,Tomohiro Masuda,Donald J. Zack,Julia E. Richards,Margaret A. Pericak-Vance,Louis R. Pasquale,Jonathan L. Haines +49 more
Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma
Gudmar Thorleifsson,G. Bragi Walters,Alex W. Hewitt,Alex W. Hewitt,Gisli Masson,Agnar Helgason,Agnar Helgason,Andrew T. DeWan,Asgeir Sigurdsson,Adalbjorg Jonasdottir,Sigurjon A. Gudjonsson,Kristinn P. Magnusson,Hreinn Stefansson,Dennis S.C. Lam,Pancy O. S. Tam,Gudrun J Gudmundsdottir,Laura Southgate,Kathryn P. Burdon,Maria Soffia Gottfredsdottir,Micheala A. Aldred,Paul Mitchell,David St Clair,David A. Collier,David A. Collier,Nelson L.S. Tang,Orn Sveinsson,Stuart MacGregor,Nicholas G. Martin,Angela J. Cree,Jane Gibson,Alex MacLeod,Aby Jacob,Sarah Ennis,Terri L. Young,Juliana C.N. Chan,W Karwatowski,Christopher J Hammond,Kristjan Thordarson,Mingzhi Zhang,Claes Wadelius,Andrew J. Lotery,Richard C. Trembath,Chi Pui Pang,Josephine Hoh,Jamie E Craig,Augustine Kong,David A. Mackey,David A. Mackey,David A. Mackey,Fridbert Jonasson,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Kari Stefansson,Kari Stefansson +53 more