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Nat Genet. 2014 Oct;46(10):1120-1125. doi: 10.1038/ng.3079. Epub 2014 Aug 31.

Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.

Author information

1
QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
2
Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
3
Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, 7000, Australia.
4
Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
5
University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
6
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
7
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
8
Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
9
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
10
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
11
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
12
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
13
MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, De Crespigny Park, London, UK.
14
Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
15
Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
16
South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
17
Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia.
18
Department of Anatomical Pathology, Flinders University, Flinders Medical Centre, South Australia.
19
Department of Ophthalmology, University of Sydney, Sydney Eye Hospital, Sydney, Australia.
20
School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia.
21
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
22
South Australian Health and Medical Research Institute, Adelaide, South Australia.
#
Contributed equally

Abstract

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

PMID:
25173105
PMCID:
PMC4177327
DOI:
10.1038/ng.3079
[Indexed for MEDLINE]
Free PMC Article

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