Journal article

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.

  • Bailey JN Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Loomis SJ Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
  • Kang JH Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Allingham RR Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
  • Gharahkhani P QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Khor CC Division of Human Genetics, Genome Institute of Singapore, Singapore.
  • Burdon KP Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
  • Aschard H Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Chasman DI Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Igo RP Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Hysi PG Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Glastonbury CA Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Ashley-Koch A Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
  • Brilliant M Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
  • Brown AA Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
  • Budenz DL Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Buil A Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
  • Cheng CY Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Choi H Section of Rheumatology and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Christen WG Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Curhan G Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • De Vivo I Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Fingert JH Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa, USA.
  • Foster PJ National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK.
  • Fuchs C Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Gaasterland D Eye Doctors of Washington, Chevy Chase, Maryland, USA.
  • Gaasterland T Scripps Genome Center, University of California at San Diego, San Diego, California, USA.
  • Hewitt AW Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
  • Hu F Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Hunter DJ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Khawaja AP Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Lee RK Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Li Z Division of Human Genetics, Genome Institute of Singapore, Singapore.
  • Lichter PR Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
  • Mackey DA Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
  • McGuffin P Medical Research Council Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK.
  • Mitchell P Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
  • Moroi SE Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
  • Perera SA Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
  • Pepper KW The Jackson Laboratory, Bar Harbor, Maine, USA.
  • Qi Q Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Realini T Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, USA.
  • Richards JE Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
  • Ridker PM Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Rimm E Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Ritch R Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.
  • Ritchie M Center for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA.
  • Schuman JS Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Scott WK Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Singh K Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA.
  • Sit AJ Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.
  • Song YE Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Tamimi RM Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Topouzis F Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
  • Viswanathan AC National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK.
  • Verma SS Center for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA.
  • Vollrath D Department of Genetics, Stanford University School of Medicine, Palo Alto, California, USA.
  • Wang JJ Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
  • Weisschuh N Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
  • Wissinger B Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
  • Wollstein G Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Wong TY Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Yaspan BL Genentech, San Francisco, California, USA.
  • Zack DJ Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, USA.
  • Zhang K Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, USA.
  • Study EN Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA.
  • Weinreb RN Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Pericak-Vance MA Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Small K Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Hammond CJ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
  • Aung T Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA.
  • Liu Y Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
  • Vithana EN QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • MacGregor S Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
  • Craig JE Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Kraft P The Jackson Laboratory, Bar Harbor, Maine, USA.
  • Howell G Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
  • Hauser MA Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
  • Pasquale LR Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Haines JL Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
  • Wiggs JL
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  • 2016-01-12
Published in:
  • Nature genetics. - 2016
English Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
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  • English
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https://folia.unifr.ch/global/documents/62571
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