New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Autor:	Springelkamp H; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands., Iglesias AI; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands., Mishra A; Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.; Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands., Höhn R; Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland.; Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany., Wojciechowski R; Computational and Statistical Genomics Branch, National Human Genome Research Institute (NIH), Baltimore, MD, USA.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA., Khawaja AP; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK., Nag A; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Wang YX; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.; Beijing Ophthalmology and Visual Science Key Lab, Beijing, China., Wang JJ; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia., Cuellar-Partida G; Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia., Gibson J; Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK., Bailey JN; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA., Vithana EN; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Gharahkhani P; Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia., Boutin T; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Ramdas WD; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands., Zeller T; Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg/Germany., Luben RN; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK., Yonova-Doing E; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Viswanathan AC; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK., Yazar S; Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia., Cree AJ; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Haines JL; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA., Koh JY; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore., Souzeau E; Department of Ophthalmology, Flinders University, Adelaide, Australia., Wilson JF; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.; Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Scotland, UK., Amin N; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands., Müller C; Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg/Germany., Venturini C; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Kearns LS; Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia., Kang JH; Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA., Tham YC; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Zhou T; Department of Ophthalmology, Flinders University, Adelaide, Australia., van Leeuwen EM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands., Nickels S; Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany., Sanfilippo P; Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.; Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia., Liao J; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., van der Linde H; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands., Zhao W; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Duke-National University of Singapore Graduate Medical School, Singapore, Singapore., van Koolwijk LM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands., Zheng L; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore., Rivadeneira F; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.; Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague, the Netherlands., Baskaran M, van der Lee SJ; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands., Perera S; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Duke-National University of Singapore Graduate Medical School, Singapore, Singapore., de Jong PT; Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.; Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.; The Netherlands Institute of Neuroscience KNAW, Amsterdam, the Netherlands., Oostra BA; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands., Uitterlinden AG; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.; Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague, the Netherlands., Fan Q; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore., Hofman A; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague, the Netherlands., Tai ES; Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.; Department of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Vingerling JR; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands., Sim X; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Wolfs RC; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands., Teo YY; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.; Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore., Lemij HG; Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, the Netherlands., Khor CC; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore., Willemsen R; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands., Lackner KJ; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany., Aung T; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Jansonius NM; Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Montgomery G; Department of Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia., Wild PS; Preventive Cardiology and Preventive Medicine/Center for Cardiology, University Medical Center Mainz, Mainz, Germany.; Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.; German Center for Cardiovascular Research (DZHK), partner site RhineMain, Mainz, Germany., Young TL; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA., Burdon KP; School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia., Hysi PG; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Pasquale LR; Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA and., Wong TY; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Klaver CC; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands., Hewitt AW; Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.; School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia., Jonas JB; Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany., Mitchell P; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia., Lotery AJ; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Foster PJ; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK., Vitart V; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Pfeiffer N; Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany., Craig JE; Department of Ophthalmology, Flinders University, Adelaide, Australia., Mackey DA; Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.; School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia., Hammond CJ; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Wiggs JL; Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA and., Cheng CY, van Duijn CM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands., MacGregor S; Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2017 Jan 15; Vol. 26 (2), pp. 438-453.
DOI:	10.1093/hmg/ddw399
Abstrakt:	Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk. (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu