title: Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.
abstract: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
authors.affiliation: Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
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authors.affiliation: Division of Human Genetics, Genome Institute of Singapore, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.|Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Kathryn P
authors.identifier: http://orcid.org/0000-0001-8217-1249
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authors.lastname: Burdon
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Hugues
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authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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authors.affiliation: Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
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authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
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authors.affiliation: Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
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authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA.
authors.forename: Epic-Norfolk Eye
authors.initials: EN
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authors.identifier: http://orcid.org/0000-0002-3227-2620
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authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
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authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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authors.identifier: http://orcid.org/0000-0002-5835-3496
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authors.affiliation: Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Jonathan L
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authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
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mesh_terms: D000067698:Ataxin-2 / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054482:Thioredoxin Reductase 2 / Q000235:genetics*
chemical_list: C000593752:ATXN2 protein, human; D000067698:Ataxin-2; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; C516127:TXNRD2 protein, human; D054482:Thioredoxin Reductase 2