Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Autor: Gharahkhani P; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Puya.Gharahkhani@qimrberghofer.edu.au., Jorgenson E; Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, USA., Hysi P; Twin Research and Genetic Epidemiology, King's College London, London, UK., Khawaja AP; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK., Pendergrass S; Geisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA., Han X; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Ong JS; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Hewitt AW; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.; Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia., Segrè AV; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Rouhana JM; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Hamel AR; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Igo RP Jr; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Choquet H; Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, USA., Qassim A; Department of Ophthalmology, Flinders University, Bedford Park, SA, Australia., Josyula NS; Geisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA., Cooke Bailey JN; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Bonnemaijer PWM; Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.; The Rotterdam Eye Hospital, Rotterdam, The Netherlands., Iglesias A; Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands., Siggs OM; Department of Ophthalmology, Flinders University, Bedford Park, SA, Australia., Young TL; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA., Vitart V; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Thiadens AAHJ; Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands., Karjalainen J; Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Uebe S; Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany., Melles RB; Department of Ophthalmology, KPNC, Redwood City, CA, USA., Nair KS; Department of Ophthalmology, School of Medicine, University of California San Francisco (UCSF), San Francisco, CA, USA., Luben R; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK., Simcoe M; Twin Research and Genetic Epidemiology, King's College London, London, UK.; Department of Ophthalmology, Kings College London, London, United Kingdom.; Institute of Ophthalmology, University College London, London, UK., Amersinghe N; University Hospital Southampton NHS Foundation Trust, Southampton, UK., Cree AJ; Faculty of Medicine, University of Southampton, Southampton, UK., Hohn R; Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, Germany.; Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany., Poplawski A; Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany., Chen LJ; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China., Rong SS; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China., Aung T; Singapore Eye Research Institute, Singapore National Eye Certre, Singapore, Singapore.; Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Vithana EN; Singapore Eye Research Institute, Singapore National Eye Certre, Singapore, Singapore.; Duke-National University of Singapore Medical School, Singapore, Republic of Singapore., Tamiya G; Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.; RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo, Japan., Shiga Y; Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan., Yamamoto M; Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan., Nakazawa T; Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.; Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.; Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.; Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan., Currant H; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK., Birney E; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK., Wang X; 23 and Me Inc., San Francisco, CA, USA., Auton A; 23 and Me Inc., San Francisco, CA, USA., Lupton MK; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Martin NG; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Ashaye A; Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria., Olawoye O; Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria., Williams SE; Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa., Akafo S; Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana., Ramsay M; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Hashimoto K; Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan., Kamatani Y; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan., Akiyama M; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Momozawa Y; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Foster PJ; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK.; UCL Institute of Ophthalmology, University College London, London, UK., Khaw PT; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK.; UCL Institute of Ophthalmology, University College London, London, UK., Morgan JE; Cardiff Centre for Vision Sciences, College of Biomedical and Life Sciences, Maindy Road, Cardiff University, Cardiff, UK., Strouthidis NG; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK.; UCL Institute of Ophthalmology, University College London, London, UK., Kraft P; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Kang JH; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Pang CP; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China., Pasutto F; Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany., Mitchell P; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia., Lotery AJ; University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Faculty of Medicine, University of Southampton, Southampton, UK., Palotie A; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Psychiatric & Neurodevelopmental Genetics Unit, Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., van Duijn C; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.; Nuffield Department of Population Health, University of Oxford, Oxford, UK., Haines JL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Hammond C; Twin Research and Genetic Epidemiology, King's College London, London, UK., Pasquale LR; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Klaver CCW; Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.; Institute for Molecular and Clinical Ophthalmology, Basel, Switzerland., Hauser M; Department of Medicine, Duke University, Durham, NC, USA.; Department of Ophthalmology, Duke University, Durham, NC, USA.; Singapore Eye Research Institute, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Khor CC; Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore., Mackey DA; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.; Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia.; Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Nedlands, WA, Australia., Kubo M; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Cheng CY; Singapore Eye Research Institute, Singapore National Eye Certre, Singapore, Singapore.; Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Craig JE; Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, SA, Australia., MacGregor S; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Wiggs JL; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Feb 24; Vol. 12 (1), pp. 1258. Date of Electronic Publication: 2021 Feb 24.
DOI: 10.1038/s41467-020-20851-4
Abstrakt: Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Databáze: MEDLINE