ArticleNature genetics2020
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05175651 (Prospective Electronic Polygenic Risk Study - Second Phase), which is not on this map. Cited by 198 papers, 12 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 12 pooled it
30.8field-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.
Prospective Electronic Polygenic Risk Study - Second Phase
Who cites it
198 citing papers in PubMed, 12 syntheses or guidelines pooled it, 343 citations in OpenAlex.
- GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology.Nature communications · 2025Pooled it
- Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.Investigative ophthalmology & visual science · 2024Pooled it
- Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.Cell reports. Medicine · 2024Pooled it
- Background polygenic risk modulates the association between glaucoma and cardiopulmonary diseases and measures: an analysis from the UK Biobank.The British journal of ophthalmology · 2023Pooled it
- The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.Nature communications · 2022Pooled it
- Glaucoma Genetic Risk Scores in the Million Veteran Program.Ophthalmology · 2022Pooled it
- High Blood Pressure and Intraocular Pressure: A Mendelian Randomization Study.Investigative ophthalmology & visual science · 2022Pooled it
- Evaluating risk for alcohol use disorder: Polygenic risk scores and family history.Alcoholism, clinical and experimental research · 2022Pooled it
- Is Genetic Risk for Sleep Apnea Causally Linked With Glaucoma Susceptibility?Investigative ophthalmology & visual science · 2022Pooled it
- Efficacy and safety of netarsudil/latanoprost fixed-dose combination vs. monotherapy in open-angle glaucoma or ocular hypertension: A systematic review and meta-analysis of randomized controlled trials.Frontiers in medicine · 2022Pooled it
- Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank.PloS one · 2022Pooled it
- Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.Nature communications · 2021Pooled it
- Association of baseline brain care score with the incidence of age-related eye diseases.Eye (London, England) · 2026Article
- An integrin beta-1-anchored bicaudal C1-polycystin-1 module essential for tubular morphogenesis in polycystic kidney disease.iScience · 2026Article
- Risk-Stratified Interventional Management and Surgical Decision-Making in Primary Glaucoma.Biomedicines · 2026Review
- Eyes of Africa: The Genetics of Blindness. Baseline characteristics, ocular features, and associations with glaucoma in continental Africans.Eye (London, England) · 2026Article
- Artificial Intelligence-Driven Multimodal Prediction of 10-Year Incident Glaucoma Integrating Genetic and Deep Learning-Derived Imaging Features.Ophthalmology science · 2026Article
- Genetic risk score to enhance glaucoma case detection: a prospective double-blind screening study (EyeLife) in the population-based Lifelines cohort.European journal of epidemiology · 2026Article
- Individuals who deviate from polygenic expectation are enriched for damaging variants in genes linked to rare disease.American journal of human genetics · 2026Article
- Transcending genome-wide association studies to create useful multi-omic views of glaucoma.Progress in retinal and eye research · 2026Review
138 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
61 authors at 20 institutions in 8 countries.
Jamie E Craig *Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Xikun Han *Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Xikun.Han@qimrberghofer.edu.au.ORCID http://orcid.org/0000-0002-3823-7308
Ayub Qassim *Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-2911-2941
Mark HassallDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-6180-7954
Jessica N Cooke BaileyDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-4001-8702
Tyler G KinzyDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Anthony P KhawajaNational Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0001-6802-8585
Jiyuan AnQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Henry MarshallDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-4425-2272
Puya GharahkhaniQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4203-5952
Robert P IgoDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-0024-1993
Stuart L GrahamFaculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-7519-969X
Paul R HealeyCentre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Jue-Sheng OngQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-6062-710X
Tiger ZhouDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Owen SiggsDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0003-2840-4851
Matthew H LawQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4303-8821
Emmanuelle SouzeauDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-2015-6577
Bronwyn RidgeDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Pirro G HysiDepartment of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK.ORCID http://orcid.org/0000-0001-5752-2510
Kathryn P BurdonMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.ORCID http://orcid.org/0000-0001-8217-1249
Richard A MillsDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
John LandersDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Jonathan B RuddleCentre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
Ashish AgarDepartment of Ophthalmology, Prince of Wales Hospital Randwick, Sydney, New South Wales, Australia.
Anna GalanopoulosSouth Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Andrew J R WhiteCentre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Colin E WilloughbyBiomedical Sciences Research Institute, Ulster University, Coleraine, UK.ORCID http://orcid.org/0000-0002-1246-4166
Nicholas H AndrewDepartment of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-1545-9231
Stephen BestEye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
Andrea L VincentDepartment of Ophthalmology, University of Auckland, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-4185-3267
Ivan GoldbergDiscipline of Ophthalmology, Faculty of Medicine and Health, University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-7180-6202
Graham Radford-SmithQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-2047-6239
Nicholas G MartinQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Grant W MontgomeryInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4140-8139
Veronique VitartMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4991-3797
Rene HoehnDepartment of Ophthalmology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland.
Robert WojciechowskiDepartment of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Jost B JonasDepartment of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0003-2972-5227
Tin AungSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Louis R PasqualeDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Angela Jane CreeClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0002-1987-8900
Sobha SivaprasadNational Institute for Health Research Moorfields Biomedical Research Centre, London, UK.
Neeru A VallabhDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
NEIGHBORHOOD consortium
UK Biobank Eye and Vision Consortium
Ananth C ViswanathanNational Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Francesca PasuttoInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Caroline C W KlaverDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2355-5258
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Robert J CassonSouth Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
Paul J FosterNational Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0002-4755-177X
Peng Tee KhawNational Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0002-8087-2268
Christopher J HammondDepartment of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK.ORCID http://orcid.org/0000-0002-3227-2620
David A MackeyMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Paul MitchellDepartment of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Andrew J LoteryClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0001-5541-4305
Janey L WiggsDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1890-3278
Alex W Hewitt *Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.ORCID http://orcid.org/0000-0002-5123-5999
Stuart MacGregor *Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-6731-8142
Flinders University · AUQIMR Berghofer Medical Research Institute · AUCase Western Reserve University · USMoorfields Eye Hospital NHS Foundation Trust · GBThe University of Sydney · AUErasmus MC · NLSt Thomas' Hospital · GBThe University of Queensland · AUUniversity of Southampton · GBUniversity of Tasmania · AUBelfast Health and Social Care Trust · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGreenlane Clinical Centre · NZHeidelberg University · DEIcahn School of Medicine at Mount Sinai · USInstitute of Genetics and Cancer · GBLions Eye Institute · AUMacquarie University · AUMassachusetts Eye and Ear Infirmary · USNational Institute for Health Research · GB
Funding
P30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Janey L Wiggs · 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
$7.9MModule 3: Gene Expression/ProteomicsP30EY031631 · NEI · AUGUSTA UNIVERSITY · PI Xingjun Fan · 2020 to 2026
$3.6MGenes and Environment Initiative in GlaucomaU01HG004728 · NHGRI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI PASQUALE, LOUIS ROBERT · 2008 to 2009
$1.0MLong Noncoding RNA lncLOXL1 and Exfoliation Syndrome.R21EY028671 · NEI · AUGUSTA UNIVERSITY · PI LIU, YUTAO · 2018 to 2019
$467kMedical Research Council MC_PC_12028Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00007/10Medical Research Council MR/T040912/1NEI NIH HHS P30 EY014104NEI NIH HHS P30 EY031631NEI NIH HHS R01 EY015473NEI NIH HHS R01 EY022305NEI NIH HHS R21 EY028671NHGRI NIH HHS U01 HG004728Wellcome Trust
Abstract
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10
Indexed as
Polymorphism, Single NucleotideAustraliaCase-Control StudiesCytoskeletal ProteinsDisease ProgressionEye ProteinsGenetic Predisposition to DiseaseGenome-Wide Association StudyGlaucomaGlycoproteinsHumansIntraocular PressureMultifactorial InheritanceMyocilinOdds RatioOptic NerveCytoskeletal ProteinsEye ProteinsGlycoproteinsMyocilin
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT05175651ClinicalTrials.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.