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Nat Genet. 2018 Jun;50(6):778-782. doi: 10.1038/s41588-018-0126-8. Epub 2018 May 21.

Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

Author information

1
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
2
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.
3
Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
4
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
5
Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK.
6
Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
7
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
8
Johns Hopkins Wilmer Eye Institute, Baltimore, MD, USA.
9
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
10
Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore.
11
Ophthalmology & Visual Sciences Academic Clinical Program (Eye-ACP), Duke-NUS Medical School, Singapore, Singapore.
12
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
13
Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK.
14
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. janey_wiggs@meei.harvard.edu.
15
Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK. chris.hammond@kcl.ac.uk.
16
Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK. pirro.hysi@kcl.ac.uk.
17
Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK. pirro.hysi@kcl.ac.uk.

Abstract

Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.

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