Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31959993
TITLE
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
ABSTRACT
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10 ). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.
DATE PUBLISHED
2020 Jan 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/05/24
accepted 2019/11/21
entrez 2020/01/22 06:00
pubmed 2020/01/22 06:00
medline 2020/01/22 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Craig JE Craig Jamie E JE Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Han X Han Xikun X School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Xikun.Han@qimrberghofer.edu.au.
Qassim A Qassim Ayub A Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Hassall M Hassall Mark M Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Cooke Bailey JN Cooke Bailey Jessica N JN Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Kinzy TG Kinzy Tyler G TG Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Khawaja AP Khawaja Anthony P AP National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
An J An Jiyuan J Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Marshall H Marshall Henry H Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Gharahkhani P Gharahkhani Puya P Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Igo RP Jr Igo Robert P RP Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Graham SL Graham Stuart L SL Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Healey PR Healey Paul R PR Clinical Ophthalmology & Eye Health, Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia.
Ong JS Ong Jue-Sheng JS Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Zhou T Zhou Tiger T Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Siggs O Siggs Owen O Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Law MH Law Matthew H MH Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Souzeau E Souzeau Emmanuelle E Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Ridge B Ridge Bronwyn B Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Hysi PG Hysi Pirro G PG Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK.
Burdon KP Burdon Kathryn P KP Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Mills RA Mills Richard A RA Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Landers J Landers John J Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Ruddle JB Ruddle Jonathan B JB Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
Agar A Agar Ashish A Department of Ophthalmology, Prince of Wales Hospital Randwick, Sydney, New South Wales, Australia.
Galanopoulos A Galanopoulos Anna A South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
White AJR White Andrew J R AJR Clinical Ophthalmology & Eye Health, Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia.
Willoughby CE Willoughby Colin E CE Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK.
Andrew NH Andrew Nicholas H NH Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Best S Best Stephen S Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
Vincent AL Vincent Andrea L AL Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
Goldberg I Goldberg Ivan I Discipline of Ophthalmology, Faculty of Medicine and Health, University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.
Radford-Smith G Radford-Smith Graham G Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Vitart V Vitart Veronique V Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Hoehn R Hoehn Rene R Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
Wojciechowski R Wojciechowski Robert R Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Jonas JB Jonas Jost B JB Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
Aung T Aung Tin T Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Pasquale LR Pasquale Louis R LR Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Cree AJ Cree Angela Jane AJ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Sivaprasad S Sivaprasad Sobha S National Institute for Health Research Moorfields Biomedical Research Centre, London, UK.
Vallabh NA Vallabh Neeru A NA St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK.
NEIGHBORHOOD consortium
UK Biobank Eye and Vision Consortium
Viswanathan AC Viswanathan Ananth C AC National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Pasutto F Pasutto Francesca F Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Haines JL Haines Jonathan L JL Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Klaver CCW Klaver Caroline C W CCW Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Casson RJ Casson Robert J RJ South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
Foster PJ Foster Paul J PJ National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Khaw PT Khaw Peng Tee PT National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Hammond CJ Hammond Christopher J CJ Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK.
Mackey DA Mackey David A DA Lions Eye Institute, Centre for Ophthalmology and Vision Sciences, University of Western Australia, Perth, Western Australia, Australia.
Mitchell P Mitchell Paul P Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Lotery AJ Lotery Andrew J AJ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Wiggs JL Wiggs Janey L JL Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Hewitt AW Hewitt Alex W AW Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
MacGregor S MacGregor Stuart S Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2020
MONTH: Jan
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R21 EY028671 NEI NIH HHS United States
1107098 Department of Health | National Health and Medical Research Council (NHMRC)
1116360 Department of Health | National Health and Medical Research Council (NHMRC)
1023911 Department of Health | National Health and Medical Research Council (NHMRC)
1116495 Department of Health | National Health and Medical Research Council (NHMRC)
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