SynthesisCommunications biology2021
A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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53citing papers in PubMed, 2 pooled it
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Mendelian randomization and genetic analyses reveal causal roles of immune cells and inflammatory proteins in keratoconus.Scientific reports · 2025Pooled it
- A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation.Communications biology · 2024Pooled it
- Article
- Paediatric Keratoconus: An ERN-EYE Clinical Consensus Statement on Diagnosis, Treatment and Follow-Up Care.Ophthalmology and therapy · 2026Review
- Deletion of ARPKD-associated Pkhd1 gene in mice results in decreased Tfap2b expression and eye abnormalities.Nature communications · 2026Article
- Article
- Oxidative Stress in Keratoconus Is Evident in Tear Fluid and Stromal Cells and Alleviated in Cell Culture by Sulforaphane.Investigative ophthalmology & visual science · 2026Article
- Influence of inflammatory and metabolic factors on keratoconus risk: a causal inference analysis.Eye (London, England) · 2026Article
- Studies of mice with a large deletion of the ARPKD-associatedbioRxiv : the preprint server for biology · 2026Article
- Short-Term Effects of Swimming Goggle Use on Anterior Segment Parameters in Patients with Keratoconus.Medicina (Kaunas, Lithuania) · 2026Article
- Uncovering pleiotropic loci linking keratoconus and allergic diseases through integrative genomic analyses.Scientific reports · 2026Article
- The Genetic and Epigenetic Architecture of Keratoconus: Emerging Pathways and Clinical Implications.Genes · 2026Review
- Tomographic Differences in Thin Corneas Following DMEK in Fuchs Dystrophy: A Case-Control Study.Ophthalmology and therapy · 2026Article
- Proteomic Analysis Provides Insights Into PPIP5K2 Function and Its Impact on Corneal Energy Metabolism.Investigative ophthalmology & visual science · 2025Article
- Oxidative-stress related increase in keratoconus tear MDA and GPX3 while NRF2-antioxidant functions decrease in stromal cells.bioRxiv : the preprint server for biology · 2025Article
- Inter-Eye Molecular Discrepancies in the Corneal Epithelium Point to TFRC in the Keratoconus Severity Signature and Mechanism of Cone Formation.Investigative ophthalmology & visual science · 2025Article
- From genomic insights to clinical care in corneal disorders.Eye (London, England) · 2025Article
- Omics in Keratoconus: From Molecular to Clinical Practice.Journal of clinical medicine · 2025Review
- Genotype-Phenotype Correlations in Corneal Dystrophies: Advances in Molecular Genetics and Therapeutic Insights.Clinical & experimental ophthalmology · 2025Review
- Genome-wide association studies, Polygenic Risk Scores and Mendelian randomisation: an overview of common genetic epidemiology methods for ophthalmic clinicians.The British journal of ophthalmology · 2025Review
Corrections and comments
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Authors and funding
62 authors.
Alison J HardcastleUCL Institute of Ophthalmology, London, UK. a.hardcastle@ucl.ac.uk.ORCID 0000-0002-0038-6770
Petra Liskova *UCL Institute of Ophthalmology, London, UK.ORCID 0000-0001-7834-8486
Yelena Bykhovskaya *The Cornea Eye Institute, Beverly Hills, CA, USA.
Bennet J McComish *Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.ORCID 0000-0003-1940-0007
Alice E Davidson *UCL Institute of Ophthalmology, London, UK.ORCID 0000-0002-1816-6151
Chris F Inglehearn *Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0002-5143-2562
Xiaohui LiInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0002-5037-3572
Hélène ChoquetDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.ORCID 0000-0001-9839-8667
Mahmoud HabeebDepartment of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
Sionne E M LucasMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Srujana SahebjadaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.ORCID 0000-0002-1945-7209
Nikolas PontikosUCL Institute of Ophthalmology, London, UK.ORCID 0000-0003-1782-4711
Karla E Rojas LopezUCL Institute of Ophthalmology, London, UK.
Anthony P KhawajaUCL Institute of Ophthalmology, London, UK.ORCID 0000-0001-6802-8585
Manir AliDivision of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0003-3204-3788
Lubica DudakovaDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Pavlina SkalickaDepartment of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Bart T H Van DoorenDepartment of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
Annette J M GeerardsThe Rotterdam Eye Hospital, Rotterdam, The Netherlands.
Christoph W HaudumDivision of Endocrinology and Diabetology, Endocrinology Lab Platform, Department of Internal Medicine, Medical University of Graz, Graz, Austria.ORCID 0000-0002-3872-5643
Valeria Lo FaroDepartment of Ophthalmology, University Medical Center Groningen (UMCG), Groningen, the Netherlands.ORCID 0000-0003-4931-7327
Abi TenenVision Eye Institute, Melbourne, VIC, Australia.
Mark J SimcoeSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.ORCID 0000-0003-2432-0810
Karina PatasovaSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
Darioush YarrandDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID 0000-0003-3570-3921
Jie YinDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Salina SiddiquiDivision of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Aine RiceDivision of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Layal Abi FarrajDivision of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0003-1484-192X
Yii-Der Ida ChenInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
Jugnoo S RahiUCL Great Ormond Street Hospital Institute of Child Health, London, UK.
Ronald M KraussOakland Research Institute, Oakland, CA, USA.
Elisabeth TheuschOakland Research Institute, Oakland, CA, USA.
Jac C CharlesworthMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Loretta Szczotka-FlynnDepartment of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA.
Carmel ToomesDivision of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Magda A Meester-SmoorDepartment of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
Andrea J RichardsonCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Paul A MitchellCentre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0002-2756-4370
Ronald B MellesDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Anthony J AldaveThe Jules Stein Institute, University of California Los Angeles, Los Angeles, CA, USA.
Richard A MillsDepartment of Ophthalmology, Flinders University, Adelaide, SA, Australia.
Ke CaoCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Elsie ChanCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Mark D DaniellCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Jie Jin WangHealth Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.ORCID 0000-0001-9491-4898
Jerome I RotterInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0001-7191-1723
Alex W HewittMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.ORCID 0000-0002-5123-5999
Stuart MacGregorQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID 0000-0001-6731-8142
Caroline C W KlaverDepartment of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.ORCID 0000-0002-2355-5258
Wishal D RamdasDepartment of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.ORCID 0000-0002-1780-5281
Jamie E CraigMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Sudha K IyengarDepartment of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA.
David O'BrartSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
Eric JorgensonDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.ORCID 0000-0002-5829-8191
Paul N BairdDepartment of Surgery, Ophthalmology, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.ORCID 0000-0002-1305-3502
Yaron S RabinowitzThe Cornea Eye Institute, Beverly Hills, CA, USA.
Kathryn P BurdonMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.ORCID 0000-0001-8217-1249
Chris J HammondSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.ORCID 0000-0002-3227-2620
Stephen J TuftUCL Institute of Ophthalmology, London, UK. s.tuft@ucl.ac.uk.ORCID 0000-0001-8192-5192
Pirro G HysiSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK. pirro.hysi@kcl.ac.uk.ORCID 0000-0001-5752-2510
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MA Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8MPharmacogenomics and Risk of Cardiovascular DiseaseU19HL069757 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI KRAUSS, RONALD M · 2010 to 2014
$12.8MGENETIC FACTORS IN KERATOCONUSR01EY009052 · NEI · CEDARS-SINAI MEDICAL CENTER · PI RABINOWITZ, YARON SOLOMON, ROTTER, JEROME I · 1993 to 2019
$10.9MGenetic Etiology of Abdominal Hernia SusceptibilityR01DK116738 · NIDDK · KAISER FOUNDATION RESEARCH INSTITUTE · PI AHITUV, NADAV, CHOQUET, HELENE · 2018 to 2020
$1.8MThe Role of Refractive Error in the Etiology of GlaucomaR01EY027004 · NEI · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHOQUET, HELENE · 2017 to 2020
$1.6MBritish Heart FoundationDepartment of HealthMedical Research Council G1002002Medical Research Council MR/S031820/1Medical Research Council MR/T040912/1NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NEI NIH HHS R01 EY009052NEI NIH HHS R01 EY027004NHLBI NIH HHS HHSN268201200008CNHLBI NIH HHS HHSN268201200008INHLBI NIH HHS U19 HL069757NIA NIH HHS RC2 AG036607NIDDK NIH HHS R01 DK116738Wellcome TrustWellcome Trust 203141/Z/16/Z
Abstract
Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.
Indexed as
Cell DifferentiationCollagenExtracellular MatrixGenetic LociKeratoconusPolymorphism, Single NucleotideAustraliaCase-Control StudiesEuropeGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypeRisk AssessmentRisk FactorsCollagen
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