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

Puya Gharahkhani; Eric Jorgenson; Pirro Hysi; Anthony P Khawaja; Sarah Pendergrass; Xikun Han; Jue Sheng Ong; Alex W Hewitt; Ayellet V Segrè; John M Rouhana; Andrew R Hamel; Robert P Igo, Jr; Helene Choquet; Ayub Qassim; Navya S Josyula; Jessica N Cooke Bailey; Pieter W M Bonnemaijer; Adriana Iglesias; Owen M Siggs; Terri L Young; Veronique Vitart; Alberta A H J Thiadens; Juha Karjalainen; Steffen Uebe; Ronald B Melles; K Saidas Nair; Robert Luben; Mark Simcoe; Nishani Amersinghe; Angela J Cree; Rene Hohn; Alicia Poplawski; Li Jia Chen; Shi-Song Rong; Tin Aung; Eranga Nishanthie Vithana; Gen Tamiya; Yukihiro Shiga; Masayuki Yamamoto; Toru Nakazawa; Hannah Currant; Ewan Birney; Xin Wang; Adam Auton; Michelle K Lupton; Nicholas G Martin; Adeyinka Ashaye; Olusola Olawoye; Susan E Williams; Stephen Akafo; Michele Ramsay; Kazuki Hashimoto; Yoichiro Kamatani; Masato Akiyama; Yukihide Momozawa; Paul J Foster; Peng T Khaw; James E Morgan; Nicholas G Strouthidis; Peter Kraft; Jae H Kang; Chi Pui Pang; Francesca Pasutto; Paul Mitchell; Andrew J Lotery; Aarno Palotie; Cornelia van Duijn; Jonathan L Haines; Chris Hammond; Louis R Pasquale; Caroline C W Klaver; Michael Hauser; Chiea Chuen Khor; David A Mackey; Michiaki Kubo; Ching-Yu Cheng; Jamie E Craig; Stuart MacGregor; Janey L Wiggs

doi:10.1038/s41467-020-20851-4

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

Journal article

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Peer reviewed

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

Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W Hewitt, Ayellet V Segrè, John M Rouhana, …

Nature communications, Vol.12(1), pp.1258-1258

2021-02-24

DOI: https://doi.org/10.1038/s41467-020-20851-4

PMID: 33627673

Abstract

Asian Continental Ancestry Group

Genetic Predisposition to Disease - genetics

Glaucoma, Open-Angle - genetics

Humans

Genetic Loci - genetics

Polymorphism, Single Nucleotide - genetics

European Continental Ancestry Group

Genotype

Genome-Wide Association Study - methods

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.

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.36 Ophthalmology; 1.36.226 Glaucoma
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Title: Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Creators: Puya Gharahkhani - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Puya.Gharahkhani@qimrberghofer.edu.au
Eric Jorgenson - Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, USA
Pirro Hysi - Twin Research and Genetic Epidemiology, King's College London, London, UK
Anthony P Khawaja - Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK
Sarah Pendergrass - Geisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA
Xikun Han - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Jue Sheng Ong - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Alex W Hewitt - Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia
Ayellet V Segrè - Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
John M Rouhana - Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
Andrew R Hamel - Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
Robert P Igo, Jr - Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Helene Choquet - Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, USA
Ayub Qassim - Department of Ophthalmology, Flinders University, Bedford Park, SA, Australia
Navya S Josyula - Geisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA
Jessica N Cooke Bailey - Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Pieter W M Bonnemaijer - The Rotterdam Eye Hospital, Rotterdam, The Netherlands
Adriana Iglesias - Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Owen M Siggs - Department of Ophthalmology, Flinders University, Bedford Park, SA, Australia
Terri L Young - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA
Veronique Vitart - Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Alberta A H J Thiadens - Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Juha Karjalainen - Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Steffen Uebe - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany
Ronald B Melles - Department of Ophthalmology, KPNC, Redwood City, CA, USA
K Saidas Nair - Department of Ophthalmology, School of Medicine, University of California San Francisco (UCSF), San Francisco, CA, USA
Robert Luben - Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK
Mark Simcoe - Institute of Ophthalmology, University College London, London, UK
Nishani Amersinghe - University Hospital Southampton NHS Foundation Trust, Southampton, UK
Angela J Cree - Faculty of Medicine, University of Southampton, Southampton, UK
Rene Hohn - Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany
Alicia Poplawski - Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany
Li Jia Chen - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
Shi-Song Rong - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
Tin Aung - Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Eranga Nishanthie Vithana - Duke-National University of Singapore Medical School, Singapore, Republic of Singapore
Gen Tamiya - RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo, Japan
Yukihiro Shiga - Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
Masayuki Yamamoto - Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
Toru Nakazawa - Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
Hannah Currant - European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK
Ewan Birney - European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK
Xin Wang - 23 and Me Inc., San Francisco, CA, USA
Adam Auton - 23 and Me Inc., San Francisco, CA, USA
Michelle K Lupton - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Nicholas G Martin - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Adeyinka Ashaye - Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria
Olusola Olawoye - Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria
Susan E Williams - Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa
Stephen Akafo - Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana
Michele Ramsay - Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Kazuki Hashimoto - Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
Yoichiro Kamatani - Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
Masato Akiyama - Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Yukihide Momozawa - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Paul J Foster - UCL Institute of Ophthalmology, University College London, London, UK
Peng T Khaw - UCL Institute of Ophthalmology, University College London, London, UK
James E Morgan - Cardiff Centre for Vision Sciences, College of Biomedical and Life Sciences, Maindy Road, Cardiff University, Cardiff, UK
Nicholas G Strouthidis - UCL Institute of Ophthalmology, University College London, London, UK
Peter Kraft - Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Jae H Kang - Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Chi Pui Pang - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
Francesca Pasutto - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany
Paul Mitchell - Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia
Andrew J Lotery - Faculty of Medicine, University of Southampton, Southampton, UK
Aarno Palotie - Broad Institute of MIT and Harvard, Cambridge, MA, USA
Cornelia van Duijn - Nuffield Department of Population Health, University of Oxford, Oxford, UK
Jonathan L Haines - Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Chris Hammond - Twin Research and Genetic Epidemiology, King's College London, London, UK
Louis R Pasquale - Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Caroline C W Klaver - Institute for Molecular and Clinical Ophthalmology, Basel, Switzerland
Michael Hauser - Duke-NUS Medical School, Singapore, Singapore
Chiea Chuen Khor - Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore
David A Mackey - Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Nedlands, WA, Australia
Michiaki Kubo - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Ching-Yu Cheng - Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Jamie E Craig - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, SA, Australia
Stuart MacGregor - QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Janey L Wiggs - Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
Publication Details: Nature communications, Vol.12(1), pp.1258-1258
Publisher: England
Grant note: R01 EY015473 / NEI NIH HHS R01 EY022891 / NEI NIH HHS MR/N003284/1 / Medical Research Council P30 EY014104 / NEI NIH HHS R21 EY028671 / NEI NIH HHS R01 EY031424 / NEI NIH HHS R01 EY018246 / NEI NIH HHS MC_PC_13048 / Medical Research Council C864/A14136 / Cancer Research UK MC-UU_12015/1 / Medical Research Council R01 EY022305 / NEI NIH HHS P30 EY031631 / NEI NIH HHS
Language: English
Resource Type: Journal article
PMID: 33627673
Record Identifier: 991031577499002976