Your browser doesn't support javascript.
loading
A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.
Hardcastle, Alison J; Liskova, Petra; Bykhovskaya, Yelena; McComish, Bennet J; Davidson, Alice E; Inglehearn, Chris F; Li, Xiaohui; Choquet, Hélène; Habeeb, Mahmoud; Lucas, Sionne E M; Sahebjada, Srujana; Pontikos, Nikolas; Lopez, Karla E Rojas; Khawaja, Anthony P; Ali, Manir; Dudakova, Lubica; Skalicka, Pavlina; Van Dooren, Bart T H; Geerards, Annette J M; Haudum, Christoph W; Faro, Valeria Lo; Tenen, Abi; Simcoe, Mark J; Patasova, Karina; Yarrand, Darioush; Yin, Jie; Siddiqui, Salina; Rice, Aine; Farraj, Layal Abi; Chen, Yii-Der Ida; Rahi, Jugnoo S; Krauss, Ronald M; Theusch, Elisabeth; Charlesworth, Jac C; Szczotka-Flynn, Loretta; Toomes, Carmel; Meester-Smoor, Magda A; Richardson, Andrea J; Mitchell, Paul A; Taylor, Kent D; Melles, Ronald B; Aldave, Anthony J; Mills, Richard A; Cao, Ke; Chan, Elsie; Daniell, Mark D; Wang, Jie Jin; Rotter, Jerome I; Hewitt, Alex W; MacGregor, Stuart.
Afiliação
  • Hardcastle AJ; UCL Institute of Ophthalmology, London, UK. a.hardcastle@ucl.ac.uk.
  • Liskova P; Moorfields Eye Hospital, NHS Foundation Trust, London, UK. a.hardcastle@ucl.ac.uk.
  • Bykhovskaya Y; UCL Institute of Ophthalmology, London, UK.
  • McComish BJ; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
  • Davidson AE; Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
  • Inglehearn CF; The Cornea Eye Institute, Beverly Hills, CA, USA.
  • Li X; Department of Surgery and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Choquet H; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • Habeeb M; UCL Institute of Ophthalmology, London, UK.
  • Lucas SEM; Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Sahebjada S; Institute 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.
  • Pontikos N; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
  • Lopez KER; Department of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
  • Khawaja AP; Department of Epidemiology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
  • Ali M; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • Dudakova L; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
  • Skalicka P; Department of Surgery, Ophthalmology, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
  • Van Dooren BTH; UCL Institute of Ophthalmology, London, UK.
  • Geerards AJM; UCL Institute of Ophthalmology, London, UK.
  • Haudum CW; UCL Institute of Ophthalmology, London, UK.
  • Faro VL; Moorfields Eye Hospital, NHS Foundation Trust, London, UK.
  • Tenen A; NIHR Biomedical Research Centre, Moorfields Eye Hospital, London, UK.
  • Simcoe MJ; Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Patasova K; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
  • Yarrand D; Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
  • Yin J; Department of Ophthalmology, Erasmus Medical Center GD, Rotterdam, The Netherlands.
  • Siddiqui S; Amphia Hospital, Breda, The Netherlands.
  • Rice A; The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
  • Farraj LA; Division of Endocrinology and Diabetology, Endocrinology Lab Platform, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
  • Chen YI; Department of Ophthalmology, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
  • Rahi JS; Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands.
  • Krauss RM; Vision Eye Institute, Melbourne, VIC, Australia.
  • Theusch E; School of Primary and Allied Health Care, Monash University, Melbourne, VIC, Australia.
  • Charlesworth JC; Melbourne Stem Cell Centre, Melbourne, VIC, 3800, Australia.
  • Szczotka-Flynn L; Section of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
  • Toomes C; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Meester-Smoor MA; Section of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
  • Richardson AJ; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Mitchell PA; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Taylor KD; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
  • Melles RB; Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Aldave AJ; Department of Ophthalmology, St James's University Hospital, Leeds, UK.
  • Mills RA; Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Cao K; Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Chan E; Institute 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.
  • Daniell MD; UCL Great Ormond Street Hospital Institute of Child Health, London, UK.
  • Wang JJ; Oakland Research Institute, Oakland, CA, USA.
  • Rotter JI; Oakland Research Institute, Oakland, CA, USA.
  • Hewitt AW; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • MacGregor S; Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA.
Commun Biol ; 4(1): 266, 2021 03 01.
Article em En | MEDLINE | ID: mdl-33649486
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.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Colágeno / Polimorfismo de Nucleotídeo Único / Matriz Extracelular / Loci Gênicos / Ceratocone País/Região como assunto: Europa / Oceania Idioma: En Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Colágeno / Polimorfismo de Nucleotídeo Único / Matriz Extracelular / Loci Gênicos / Ceratocone País/Região como assunto: Europa / Oceania Idioma: En Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Reino Unido