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Nat Genet. 2014 Oct;46(10):1126-1130. doi: 10.1038/ng.3087. Epub 2014 Aug 31.

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.

Author information

1
Department of Twin Research and Genetic Epidemiology, King's College London, UK.
2
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
3
Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
4
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
5
Duke-National University of Singapore, Graduate Medical School, Singapore.
6
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
7
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
8
Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029.
9
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
10
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and, Baltimore, MD, USA.
11
National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA.
12
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh.
13
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia.
14
Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
15
Institute of Ophthalmology, University College London, UK.
16
deCODE/Amgen, 101 Reykjavik, Iceland.
17
Division of Human Genetics, Genome Institute of Singapore, Singapore.
18
Eye Clinic, 105 Reykjavik, Iceland.
19
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730.
20
Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany.
21
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
22
NHS Princess Alexandra Eye Pavilion, Edinburgh, UK.
23
Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany.
24
Department of Statistics and Applied Probability, National University of Singapore, Singapore.
25
Duke University, Duke Eye Center, Durham, NC, USA.
26
Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
27
Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany.
28
Inserm, UMR774, Lille, France.
29
Université Lille 2, Lille, France.
30
Institut Pasteur de Lille, France.
31
Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK.
32
Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA.
33
Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland.
34
Human Genetics & Genomic Medicine, Faulty of Medicine, University of Southampton, UK.
35
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
36
Genetic Epidemiology, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia.
37
Department of Ophthalmology, University Medical Center Groningen, the Netherlands.
38
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
39
Department of Medicine, National University of Singapore and National University Health System, Singapore.
40
Centre Hospitalier Régional Universitaire de Lille, France.
41
Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK.
42
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
43
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
44
The University of Queensland, Diamantina Institute, Woollongabba, Australia.
45
Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
46
Department of Ophthalmology, Flinders University, Adelaide, Australia.
47
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
48
Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
49
Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany.
50
Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
51
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
52
Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.
53
School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
54
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
55
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
56
Univ. Bordeaux, ISPED, Bordeaux, France.
57
Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France.
58
Glaucoma Service, the Rotterdam Eye Hospital, Rotterdam, the Netherlands.
59
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
#
Contributed equally

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.

PMID:
25173106
PMCID:
PMC4177225
DOI:
10.1038/ng.3087
[Indexed for MEDLINE]
Free PMC Article

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