SynthesisNature genetics2016
Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.
Registry-linked trialOpen access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000125 (Ocular Hypertension Treatment Study), which is not on this map. Cited by 155 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 8 pooled it
33.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Ocular Hypertension Treatment Study (OHTS)
Who cites it
155 citing papers in PubMed, 8 syntheses or guidelines pooled it, 272 citations in OpenAlex.
- Association of Gene Polymorphisms with Normal Tension Glaucoma: A Systematic Review and Meta-Analysis.Genes · 2024Pooled it
- Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.Cell reports. Medicine · 2024Pooled it
- Glaucoma Genetic Risk Scores in the Million Veteran Program.Ophthalmology · 2022Pooled it
- Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.Nature communications · 2021Pooled it
- Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.Investigative ophthalmology & visual science · 2020Pooled it
- A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nature communications · 2018Pooled it
- Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.Nature genetics · 2018Pooled it
- Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis.Medicine · 2017Pooled it
- Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.Human genetics · 2018Trial
- Decoding Primary Open-Angle Glaucoma: A Multi-Omics Approach to Identify Druggable Effector Genes.Investigative ophthalmology & visual science · 2026Article
- A Primary Open-Angle Glaucoma Locus Near Transcription FactorOphthalmology science · 2026Article
- Transcending genome-wide association studies to create useful multi-omic views of glaucoma.Progress in retinal and eye research · 2026Review
- Primary Open-Angle Glaucoma among Black and Latinx Populations: Exploring Racial Disparities in the United States.Journal of racial and ethnic health disparities · 2026Review
- Txnrd2 loss in skeletal muscle causes muscle atrophy and drives leanness and obesity resistance.Redox biology · 2026Article
- Genetic Risk Factors and Clinical Implications of Glaucoma in the Saudi Population: A Review.International journal of molecular sciences · 2026Review
- Variant-to-gene mapping identifiesbioRxiv : the preprint server for biology · 2026Article
- Deep-learning-derived glaucoma-related endophenotypes enable novel genome-wide genetic and functional discovery.Research square · 2026Article
- Article
- Genetic Architecture and Clinical Phenotypes of Primary Open-Angle Glaucoma: An Updated Review of Mendelian Genes, GWAS Loci, and Polygenic Risk.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Experimental models to study oxidative stress in glaucoma: integratingFrontiers in pharmacology · 2026Review
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
82 authors at 20 institutions in 7 countries.
Jessica N Cooke BaileyDepartment of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.ORCID http://orcid.org/0000-0002-4001-8702
Stephanie J LoomisDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Jae H KangChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0003-4812-0557
R Rand AllinghamDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
Puya GharahkhaniQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4203-5952
Chiea Chuen KhorDivision of Human Genetics, Genome Institute of Singapore, Singapore.
Kathryn P BurdonMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.ORCID http://orcid.org/0000-0001-8217-1249
Hugues AschardDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Robert P IgoDepartment of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Pirro G HysiDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Craig A GlastonburyDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Allison Ashley-KochDepartment of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Murray BrilliantCenter for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
Andrew A BrownDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Donald L BudenzDepartment of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA.
Alfonso BuilDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Ching-Yu ChengDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hyon ChoiSection of Rheumatology and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA.
William G ChristenDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Gary CurhanChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Immaculata De VivoChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
John H FingertDepartment of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa, USA.
Paul J FosterNational Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK.
Charles FuchsChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Douglas GaasterlandEye Doctors of Washington, Chevy Chase, Maryland, USA.
Terry GaasterlandScripps Genome Center, University of California at San Diego, San Diego, California, USA.
Alex W HewittCentre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
Frank HuDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
David J HunterDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Anthony P KhawajaDepartment of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.ORCID http://orcid.org/0000-0001-6802-8585
Richard K LeeBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Zheng LiDivision of Human Genetics, Genome Institute of Singapore, Singapore.ORCID http://orcid.org/0000-0002-7060-2213
Paul R LichterDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
David A MackeyMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Peter McGuffinMedical Research Council Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK.
Paul MitchellCentre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
Sayoko E MoroiDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Shamira A PereraSingapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Keating W PepperThe Jackson Laboratory, Bar Harbor, Maine, USA.
Qibin QiDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Tony RealiniDepartment of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, USA.
Julia E RichardsDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0003-4808-5931
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Eric RimmChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Robert RitchEinhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.ORCID http://orcid.org/0000-0002-9368-7547
Marylyn RitchieCenter for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-1208-1720
Joel S SchumanDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-8885-3766
William K ScottInstitute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Kuldev SinghDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA.
Arthur J SitDepartment of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.
Yeunjoo E SongDepartment of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Rulla M TamimiChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Fotis TopouzisDepartment of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
Ananth C ViswanathanNational Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK.
Shefali Setia VermaCenter for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA.
Douglas VollrathDepartment of Genetics, Stanford University School of Medicine, Palo Alto, California, USA.
Jie Jin WangCentre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
Nicole WeisschuhInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Bernd WissingerInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Gadi WollsteinDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Tien Y WongDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Brian L YaspanGenentech, San Francisco, California, USA.
Donald J ZackWilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, USA.
Kang ZhangHamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, USA.
Epic-Norfolk Eye StudyDepartment of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA.
ANZRAG Consortium
Robert N WeinrebHamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, USA.
Margaret A Pericak-VanceInstitute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Kerrin SmallDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Christopher J HammondDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-3227-2620
Tin AungSingapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Yutao LiuDepartment of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA.
Eranga N VithanaSingapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Stuart MacGregorQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Jamie E CraigDepartment of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Peter KraftDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Gareth HowellThe Jackson Laboratory, Bar Harbor, Maine, USA.
Michael A HauserDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
Louis R PasqualeDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0002-5835-3496
Jonathan L HainesDepartment of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Janey L WiggsDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USNational University of Singapore · SGKing's College London · GBHarvard University · USUniversity School · USDuke Medical Center · USUniversity of Miami · USUniversity of Michigan · USAugusta University · USJackson Laboratory · USMassachusetts Eye and Ear Infirmary · USNational Institute for Health Research · GBPennsylvania State University · USQIMR Berghofer Medical Research Institute · AUStanford University · USSTZ eyetrial · DEThe University of Sydney · AUUniversity of Geneva · CHUniversity of Pittsburgh · USUniversity of San Diego · US
Funding
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2MP30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Eric A Pierce · 2002 to 2026
$15.1MGene-Environment Interactions in GlaucomaR01EY015473 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI PASQUALE, LOUIS ROBERT · 2005 to 2021
$8.3MThe NEIGHBORHOOD: POAG Heritable Overall Operational DatabaseR01EY022305 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI WIGGS, JANEY L · 2012 to 2025
$7.9MInstitutional Clinical and Translational Science AwardKL2TR000428 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$6.2MFAMILIAL PRIMARY OPEN ANGLE GLAUCOMAR01EY010886 · NEI · TUFTS MEDICAL CENTER · PI WIGGS, JANEY L · 1995 to 2004
$4.7MIRIS: Incorporating Research Into SightU01HG006389 · NHGRI · ESSENTIA INSTITUTE OF RURAL HEALTH · PI MCCARTY, CATHERINE ANNE · 2011 to 2014
$4.1MThe Women's Health Study: Infrastructure Support for Continued Cohort Follow-upUM1CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2014 to 2018
$4.0MGenetic Etiologies of Primary Open Angle GlaucomaR01EY015872 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI WIGGS, JANEY L · 2005 to 2009
$3.3MMolecular Genetics of Norma Tension GlaucomaR01EY023512 · NEI · UNIVERSITY OF IOWA · PI FINGERT, JOHN H, MULLINS, ROBERT FOSTER · 2014 to 2017
$1.8MDual Leucine Zipper Kinase (DLK) as a Mediator of Retinal Ganglion Cell InjuryR01EY023754 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZACK, DONALD J. · 2013 to 2016
$1.6MGenomes in Eye Disease: Methods to Query Variants Across Multiple Genome-wide DatR01EY022306 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAASTERLAND, THERESA · 2012 to 2014
$1.0MCancer Research UK C864/A14136Department of Health SRF/01/010Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MR/K006584/1NCATS NIH HHS KL2 TR000428NCATS NIH HHS UL1 TR000427NCI NIH HHS UM1 CA182913NEI NIH HHS P30 EY014104NEI NIH HHS R01 EY010886NEI NIH HHS R01 EY015473NEI NIH HHS R01 EY015872NEI NIH HHS R01 EY022305NEI NIH HHS R01EY022305NEI NIH HHS R01 EY022306NEI NIH HHS R01 EY023512NEI NIH HHS R01 EY023754NHGRI NIH HHS U01 HG006389Wellcome Trust
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.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyAtaxin-2Forkhead Transcription FactorsGlaucoma, Open-AngleHumansPolymorphism, Single NucleotideThioredoxin Reductase 2Ataxin-2ATXN2 protein, humanForkhead Transcription FactorsFOXC1 protein, humanThioredoxin Reductase 2TXNRD2 protein, human
Identifiers
What OpenQuestion holds
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Read underepoch 390
Registered trials
NCT00000125ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.