Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma.

Autor: Diaz-Torres S; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Santiago.DiazTorres@qimrberghofer.edu.au.; Faculty of Medicine, University of Queensland (UQ), Brisbane, QLD, Australia. Santiago.DiazTorres@qimrberghofer.edu.au., He W; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, University of Queensland (UQ), Brisbane, QLD, Australia., Yu R; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Khawaja AP; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK., Hammond CJ; Department of Ophthalmology, King's College London, London, UK.; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Hysi PG; Department of Ophthalmology, King's College London, London, UK.; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Pasquale LR; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Wu Y; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Kubo M; RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan., Akiyama M; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan., Aung T; Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, 169857, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore., Cheng CY; Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, 169857, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore., Khor CC; Division of Human Genetics, Genome Institute of Singapore, Singapore, 138672, Singapore., Kraft P; Harvard School of Public Health, Boston, MA, 02114, USA., Kang JH; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Hewitt AW; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia., Mackey DA; Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia., Craig JE; Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, Australia., Wiggs JL; Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA., Ong JS; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., MacGregor S; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, University of Queensland (UQ), Brisbane, QLD, Australia., Gharahkhani P; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Puya.Gharahkhani@qimrberghofer.edu.au.; Faculty of Medicine, University of Queensland (UQ), Brisbane, QLD, Australia. Puya.Gharahkhani@qimrberghofer.edu.au.; School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, Australia. Puya.Gharahkhani@qimrberghofer.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 17; Vol. 15 (1), pp. 9959. Date of Electronic Publication: 2024 Nov 17.
DOI: 10.1038/s41467-024-54301-2
Abstrakt: Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. We conducted a comprehensive multi-ethnic meta-analysis, prioritized variants based on functional annotation, and explored drug-gene interactions. We further assessed the genetic overlap between NTG and HTG using pairwise GWAS analysis. We identified 22 risk loci associated with NTG, 17 of which have not previously been reported for NTG. Two loci, BMP4 and TBKBP1, have not previously been associated with glaucoma at the genome-wide significance level. Our results indicate that while there is a significant overlap in risk loci between tension subtypes, the magnitude of the effect tends to be lower in NTG compared to HTG, particularly for IOP-related loci. Additionally, we identified a potential role for biologic immunomodulatory treatments as neuroprotective agents.
Competing Interests: Competing interests A.P.K. has acted as a paid consultant or lecturer to Abbvie, Aerie, Allergan, Google Health, Heidelberg Engineering, Novartis, Reichert, Santen and Thea. J.H.K. has received research funding from Pfizer, Inc. S.M., J.E.C. and A.W.H. are co-founders of and hold stock in Seonix Pty Ltd. The remaining authors report no other competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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