title: Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.
abstract: Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Duke-National University of Singapore, Graduate Medical School, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Henriët
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authors.affiliation: Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029.
authors.forename: Stuart
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authors.lastname: Macgregor
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jessica N Cooke
authors.initials: JNC
authors.lastname: Bailey
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and, Baltimore, MD, USA.|National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Robert
authors.initials: R
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authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh.
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Nag
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Höhn
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.|Institute of Ophthalmology, University College London, UK.
authors.forename: Cristina
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authors.lastname: Venturini
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
authors.forename: Alireza
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.affiliation: deCODE/Amgen, 101 Reykjavik, Iceland.
authors.forename: Gudmar
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authors.lastname: Thorleifsson
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.|Duke-National University of Singapore, Graduate Medical School, Singapore.
authors.forename: Eranga
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authors.lastname: Vithana
authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.|Division of Human Genetics, Genome Institute of Singapore, Singapore.
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authors.initials: CC
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authors.affiliation: Eye Clinic, 105 Reykjavik, Iceland.
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authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
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authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jonathan L
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.initials: YX
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authors.affiliation: Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany.
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authors.initials: PS
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authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
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authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
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authors.initials: SE
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authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore.
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authors.initials: YY
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authors.initials: G
authors.lastname: Cuellar-Partida
authors.affiliation: Duke University, Duke Eye Center, Durham, NC, USA.
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authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.affiliation: Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
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authors.affiliation: Inserm, UMR774, Lille, France.|Université Lille 2, Lille, France.|Institut Pasteur de Lille, France.
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authors.initials: C
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authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.initials: AI
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authors.initials: EM
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authors.affiliation: Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland.
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authors.affiliation: deCODE/Amgen, 101 Reykjavik, Iceland.
authors.forename: Unnur
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.initials: DDG
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authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
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authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, the Netherlands.
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authors.lastname: Yazar
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Duke-National University of Singapore, Graduate Medical School, Singapore.|Department of Medicine, National University of Singapore and National University Health System, Singapore.
authors.forename: E-Shyong
authors.initials: ES
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authors.affiliation: Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany.|Inserm, UMR774, Lille, France.|Université Lille 2, Lille, France.|Centre Hospitalier Régional Universitaire de Lille, France.
authors.forename: Philippe
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authors.affiliation: Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK.
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authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
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authors.affiliation: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.|Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.
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authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
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authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
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authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Duke-National University of Singapore, Graduate Medical School, Singapore.
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authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.lastname: Vingerling
authors.affiliation: Univ. Bordeaux, ISPED, Bordeaux, France.|Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Maubaret
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.affiliation: Glaucoma Service, the Rotterdam Eye Hospital, Rotterdam, the Netherlands.
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authors.affiliation: Duke University, Duke Eye Center, Durham, NC, USA.
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authors.forename: Louis R
authors.initials: LR
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authors.affiliation: Univ. Bordeaux, ISPED, Bordeaux, France.|Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France.
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authors.initials: C
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authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
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authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
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authors.initials: CCW
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authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
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authors.initials: KS
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authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, Australia.
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authors.affiliation: deCODE/Amgen, 101 Reykjavik, Iceland.
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authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
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authors.affiliation: NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Ananth
authors.initials: A
authors.lastname: Viswanathan
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia.|Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.affiliation: Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
authors.forename: Janey L
authors.initials: JL
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authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
authors.forename: Christopher J
authors.initials: CJ
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authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005353:Fibronectins / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D005901:Glaucoma / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; D000017:ABO Blood-Group System; D064286:ATP Binding Cassette Transporter 1; C543006:FNDC3B protein, human; D005353:Fibronectins