Genetic Epidemiology, Psychiatric Genetics, Asthma 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
aheadofprint 2014/08/31
entrez 2014/09/01 06:00
pubmed 2014/09/01 06:00
medline 2014/12/17 06:00
pmc-release 2015/04/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gharahkhani P Gharahkhani Puya P 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. [2].
Burdon KP Burdon Kathryn P KP 1] Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. [2] Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. [3].
Fogarty R Fogarty Rhys R Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Sharma S Sharma Shiwani S Department of Ophthalmology, Flinders University, Adelaide, South Australia, 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, South Australia, Australia.
Law MH Law Matthew H MH QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Cremin K Cremin Katie K University of Queensland Diamantina Institute, Brisbane, Queensland, Australia.
Bailey JN Bailey Jessica N Cooke JN 1] Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] 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 1] Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Haines JL Haines Jonathan L JL 1] Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Hauser MA Hauser Michael A MA 1] Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA. [2] Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Viswanathan AC Viswanathan Ananth C AC National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London (UCL) Institute of Ophthalmology, London, UK.
McGuffin P McGuffin Peter P Medical Research Council (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 National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London (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, New South Wales, Australia.
Zhou T Zhou Tiger T Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Souzeau E Souzeau Emmanuelle E Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Landers J Landers John J Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Fitzgerald JT Fitzgerald Jude T JT Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Klebe S Klebe Sonja S Department of Anatomical Pathology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, 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, New South Wales, Australia.
Healey PR Healey Paul R PR Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
Wellcome Trust Case Control Consortium 2
NEIGHBORHOOD Consortium
Mills RA Mills Richard A RA Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Wang JJ Wang Jie Jin JJ Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Radford-Smith G Radford-Smith Graham G 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. [2] School of Medicine, University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
Whiteman DC Whiteman David C DC QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Brown MA Brown Matthew A MA University of Queensland Diamantina Institute, Brisbane, Queensland, 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 1] Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. [2] Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia.
Mitchell P Mitchell Paul P Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia.
MacGregor S MacGregor Stuart S 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. [2].
Craig JE Craig Jamie E JE 1] Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. [2] South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. [3].
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
P30 EY014104 NEI NIH HHS United States
R01 CA001833 NCI NIH HHS United States
R01 CA136725 NCI NIH HHS United States
R01 EY015473 NEI NIH HHS United States
R01 EY022305 NEI NIH HHS United States
U01 HG004728 NHGRI 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
NIHMS619477 [Available on 04/01/15] NLM
PMC4177327 [Available on 04/01/15] NLM