Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25173105
TITLE
Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
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.
DATE PUBLISHED
2014 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/04/09
accepted 2014/08/04
entrez 2014/09/01 06:00
pubmed 2014/09/01 06:00
medline 2014/12/17 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gharahkhani P Gharahkhani Puya P QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Burdon KP Burdon Kathryn P KP Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, 7000, Australia.
Fogarty R Fogarty Rhys R Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Sharma S Sharma Shiwani S Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Hewitt AW Hewitt Alex W AW Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Martin S Martin Sarah S Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Law MH Law Matthew H MH QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Cremin K Cremin Katie K University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
Bailey JNC Bailey Jessica N Cooke JNC Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Loomis SJ Loomis Stephanie J SJ Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Pasquale LR Pasquale Louis R LR Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Haines JL Haines Jonathan L JL Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Hauser MA Hauser Michael A MA Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Viswanathan AC Viswanathan Ananth C AC NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
McGuffin P McGuffin Peter P MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, De Crespigny Park, London, UK.
Topouzis F Topouzis Fotis F Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
Foster PJ Foster Paul J PJ NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Graham SL Graham Stuart L SL Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
Casson RJ Casson Robert J RJ South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
Chehade M Chehade Mark M South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
White AJ White Andrew J AJ Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia.
Zhou T Zhou Tiger T Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Souzeau E Souzeau Emmanuelle E Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Landers J Landers John J Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Fitzgerald JT Fitzgerald Jude T JT Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Klebe S Klebe Sonja S Department of Anatomical Pathology, Flinders University, Flinders Medical Centre, South Australia.
Ruddle JB Ruddle Jonathan B JB Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Goldberg I Goldberg Ivan I Department of Ophthalmology, University of Sydney, Sydney Eye Hospital, Sydney, Australia.
Healey PR Healey Paul R PR Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia.
Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD consortium
Mills RA Mills Richard A RA Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia.
Wang JJ Wang Jie Jin JJ Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
RadfordSmith G RadfordSmith Graham G School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia.
Whiteman DC Whiteman David C DC QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Brown MA Brown Matthew A MA University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
Wiggs JL Wiggs Janey L JL Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Mackey DA Mackey David A DA Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
Mitchell P Mitchell Paul P Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia.
MacGregor S MacGregor Stuart S QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Craig JE Craig Jamie E JE South Australian Health and Medical Research Institute, Adelaide, South Australia.
INVESTIGATORS
JOURNAL
VOLUME: 46
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2014
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
U01 HG004728 NHGRI NIH HHS United States
R01 CA001833 NCI NIH HHS United States
G1000143 Medical Research Council United Kingdom
R01 CA136725 NCI NIH HHS United States
G0401527 Medical Research Council United Kingdom
R01 EY022305 NEI NIH HHS United States
084620 Wellcome Trust United Kingdom
R01 EY015473 NEI NIH HHS United States
MR/K006584/1 Medical Research Council United Kingdom
P30 EY014104 NEI NIH HHS United States
R01 EY023512 NEI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
ATP Binding Cassette Transporter 1 metabolism
Aged metabolism
Aged, 80 and over metabolism
Australia metabolism
Cohort Studies metabolism
Female metabolism
Gene Expression metabolism
Gene Frequency metabolism
Genetic Predisposition to Disease genetics
Genotype genetics
Glaucoma, Open-Angle metabolism
Humans metabolism
Hydro-Lyases genetics
Immunoblotting genetics
Male genetics
Meta-Analysis as Topic genetics
Microfilament Proteins metabolism
Middle Aged metabolism
Polymorphism, Single Nucleotide metabolism
Reverse Transcriptase Polymerase Chain Reaction metabolism
Risk Factors metabolism
United States metabolism
SUPPLEMENTARY MESH
SUPPLMESHNAME SUPPLMESHTYPE
Glaucoma, Primary Open Angle Disease
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 ABCA1 protein, human
0 AFAP1 protein, human
0 ATP Binding Cassette Transporter 1
0 Microfilament Proteins
EC 4.2.1.- Hydro-Lyases
EC 4.2.1.47 GDPmannose 4,6-dehydratase
OTHER ID's
OTHERID SOURCE
EMS59932 NLM
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