New Results
A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease
View ORCID ProfilePuya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P. Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W. Hewitt, Ayellet Segre, Robert P. Igo Jr, Helene Choquet, Ayub Qassim, Navya S Josyula, Jessica N. Cooke Bailey, Pieter Bonnemaijer, Adriana Iglesias, View ORCID ProfileOwen M. Siggs, Terri 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 (CUHK), Ching-Yu Cheng, Eranga Nishanthie Vithana, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23andMe Research Team, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, John Rouhana, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Adeyinka Ashaye, Olusola Olawoye, Susan E. Williams, Stephen Akafo, Michele Ramsay, Kazuki Hashimoto, Yoichito Kamatani, Masato Akiama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae Hee Kang, Calvin Chi Pui Pang (CUHK), Francesca Pasutto, Paul Mitchell, Andrew J. Lotery, Aarno Palotie, Cornelia van Duijn, Jonathan Haines, Chris Hammond, Louis R. Pasquale, Caroline C.W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Tin Aung, Jamie Craig, Stuart MacGregor, Janey Wiggs
doi: https://doi.org/10.1101/2020.01.30.927822
Puya Gharahkhani
1QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4029, Australia
Eric Jorgenson
2Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA 94612, USA
Pirro Hysi
3Twin Research and Genetic Epidemiology, King’s College London, London, UK
Anthony P. Khawaja
4NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
5Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK
Sarah Pendergrass
6Geisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA
Xikun Han
1QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4029, Australia
Jue Sheng Ong
1QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4029, Australia
Alex W. Hewitt
7Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
8Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia
Ayellet Segre
9Department of Ophthalmology, Harvard Medical School, Boston, Mass USA 02114
Robert P. Igo Jr
10Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
Helene Choquet
2Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA 94612, USA
Ayub Qassim
11Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia
Navya S Josyula
12Geisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA
Jessica N. Cooke Bailey
10Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
13Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
Pieter Bonnemaijer
14Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands
15Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands
16The Rotterdam Eye Hospital, Rotterdam, The Netherlands
Adriana Iglesias
14Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands
15Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands
17Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Owen M. Siggs
11Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia
Terri Young
18Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
Veronique Vitart
19Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Alberta A.H.J. Thiadens
14Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands
15Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands
Juha Karjalainen
20Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland
21Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA
22Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Steffen Uebe
23Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany
Ronald B. Melles
24Department of Ophthalmology, KPNC, Redwood City, CA 94063, USA
K. Saidas Nair
25Department of Ophthalmology, and Department of Anatomy, School of Medicine, University of California San Francisco (UCSF), San Francisco, CA 94143, USA
Robert Luben
5Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK
Mark Simcoe
3Twin Research and Genetic Epidemiology, King’s College London, London, UK
Nishani Amersinghe
26University Hospital Southampton NHS Foundation Trust, Southampton, UK
Angela J. Cree
27Faculty of Medicine, University of Southampton, Southampton, UK
Rene Hohn
28Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, Germany
29Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany
Alicia Poplawski
30IMBEI Institute of Medical Biostatistics, Epidemiology and Informatics University Medicine of the Johannes Gutenberg University, Mainz, Germany
Li Jia Chen (CUHK)
31The Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
Ching-Yu Cheng
32Singapore Eye Research Institute, Singapore National Eye Certre, Singapore 169856, Singapore
33Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
34Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Eranga Nishanthie Vithana
32Singapore Eye Research Institute, Singapore National Eye Certre, Singapore 169856, Singapore
35Duke-National University of Singapore Medical School, Singapore, Republic of Singapore
Gen Tamiya
36Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
37RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan
Yukihiro Shiga
38Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
Masayuki Yamamoto
36Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Toru Nakazawa
38Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
39Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
40Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan,
41Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
John Rouhana
9Department of Ophthalmology, Harvard Medical School, Boston, Mass USA 02114
Hannah Currant
42European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom,
Ewan Birney
42European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom,
Xin Wang
4323andMe Inc., San Francisco, California, USA
Adam Auton
4323andMe Inc., San Francisco, California, USA
Adeyinka Ashaye
44Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria
Olusola Olawoye
44Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria
Susan E. Williams
45Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa
Stephen Akafo
46Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana
Michele Ramsay
47Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Kazuki Hashimoto
38Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
Yoichito Kamatani
48Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
49Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan
Masato Akiama
48Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
50Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yukihide Momozawa
51Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
Paul J. Foster
52National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK
53UCL Institute of Ophthalmology, University College London, London, United Kingdom
Peng T. Khaw
52National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK
53UCL Institute of Ophthalmology, University College London, London, United Kingdom
James E. Morgan
54Cardiff Centre for Vision Sciences, College of Biomedical and Life Sciences, Maindy Road, Cardiff University, Cardiff, UK
Nicholas G. Strouthidis
52National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, UK
53UCL Institute of Ophthalmology, University College London, London, United Kingdom
Peter Kraft
55Harvard School of Public Health, Boston, MA, 02114, USA
Jae Hee Kang
56Channing Division of Network Medicine, Brigham and Women’s Hospital / Harvard Medical School, Boston, MA, 02114, USA
Calvin Chi Pui Pang (CUHK)
57The Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Peoples Republic of China
Francesca Pasutto
23Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany
Paul Mitchell
58Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, NSW 2145, Sydney, NSW, Australia
Andrew J. Lotery
26University Hospital Southampton NHS Foundation Trust, Southampton, UK
Aarno Palotie
59Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
60Analytical and Translational Genetics Unit (ATGU), Psychiatric & Neurodevelopmental Genetics Unit, Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA, USA
61Broad Institute of MIT and Harvard, Cambridge, MA, USA
Cornelia van Duijn
15Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands
Jonathan Haines
10Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
13Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
Chris Hammond
3Twin Research and Genetic Epidemiology, King’s College London, London, UK
Louis R. Pasquale
62Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Caroline C.W. Klaver
14Depatment of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands
15Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands
63Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands
64Institute for Molecular and Clinical Ophthalmology, Basel, Switzerland
Michael Hauser
65Department of Medicine, Duke University, Durham, North Carolina
66Department of Ophthalmology, Duke University, Durham, North Carolina
67Singapore Eye Research Institute, Singapore; Duke-NUS Medical School, Signapore
Chiea Chuen Khor
68Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore
David A. Mackey
69Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute
8Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia
7Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
Michiaki Kubo
70RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
Tin Aung
32Singapore Eye Research Institute, Singapore National Eye Certre, Singapore 169856, Singapore
33Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
34Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Jamie Craig
71Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, Australia
Stuart MacGregor
1QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4029, Australia
Janey Wiggs
9Department of Ophthalmology, Harvard Medical School, Boston, Mass USA 02114
Abstract
We conducted a large multi-ethnic meta-analysis of genome-wide association studies for primary open-angle glaucoma (POAG) on a total of 34,179 cases vs 349,321 controls, and identified 127 independent risk loci, almost doubling the number of known loci for POAG. The majority of loci have broadly consistent effect across European, Asian and African ancestries. We identify a link, both genome-wide and at specific loci, between POAG and Alzheimer’s disease. Gene expression data and bioinformatic functional analyses provide further support for the functional relevance of the POAG risk genes. Several drug compounds target these risk genes and may be potential candidates for developing novel POAG treatments.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Posted February 03, 2020.
A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease
Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P. Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W. Hewitt, Ayellet Segre, Robert P. Igo Jr, Helene Choquet, Ayub Qassim, Navya S Josyula, Jessica N. Cooke Bailey, Pieter Bonnemaijer, Adriana Iglesias, Owen M. Siggs, Terri 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 (CUHK), Ching-Yu Cheng, Eranga Nishanthie Vithana, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23andMe Research Team, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, John Rouhana, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Adeyinka Ashaye, Olusola Olawoye, Susan E. Williams, Stephen Akafo, Michele Ramsay, Kazuki Hashimoto, Yoichito Kamatani, Masato Akiama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae Hee Kang, Calvin Chi Pui Pang (CUHK), Francesca Pasutto, Paul Mitchell, Andrew J. Lotery, Aarno Palotie, Cornelia van Duijn, Jonathan Haines, Chris Hammond, Louis R. Pasquale, Caroline C.W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Tin Aung, Jamie Craig, Stuart MacGregor, Janey Wiggs
bioRxiv 2020.01.30.927822; doi: https://doi.org/10.1101/2020.01.30.927822
A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease
Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P. Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W. Hewitt, Ayellet Segre, Robert P. Igo Jr, Helene Choquet, Ayub Qassim, Navya S Josyula, Jessica N. Cooke Bailey, Pieter Bonnemaijer, Adriana Iglesias, Owen M. Siggs, Terri 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 (CUHK), Ching-Yu Cheng, Eranga Nishanthie Vithana, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23andMe Research Team, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, John Rouhana, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Adeyinka Ashaye, Olusola Olawoye, Susan E. Williams, Stephen Akafo, Michele Ramsay, Kazuki Hashimoto, Yoichito Kamatani, Masato Akiama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae Hee Kang, Calvin Chi Pui Pang (CUHK), Francesca Pasutto, Paul Mitchell, Andrew J. Lotery, Aarno Palotie, Cornelia van Duijn, Jonathan Haines, Chris Hammond, Louis R. Pasquale, Caroline C.W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Tin Aung, Jamie Craig, Stuart MacGregor, Janey Wiggs
bioRxiv 2020.01.30.927822; doi: https://doi.org/10.1101/2020.01.30.927822
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