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PMID |
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TITLE |
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Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma. |
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ABSTRACT |
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Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2017/08/23 |
accepted |
2018/01/18 |
entrez |
2018/02/17 06:00 |
pubmed |
2018/02/17 06:00 |
medline |
2019/10/30 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Gharahkhani P |
|
Gharahkhani |
Puya |
P |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Puya.Gharahkhani@qimrberghofer.edu.au. |
Burdon KP |
|
Burdon |
Kathryn P |
KP |
|
University of Tasmania, Hobart, Tasmania, Australia. |
Cooke Bailey JN |
|
Cooke Bailey |
Jessica N |
JN |
|
Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. |
Hewitt AW |
|
Hewitt |
Alex W |
AW |
|
University of Tasmania, Hobart, Tasmania, Australia. |
Law MH |
|
Law |
Matthew H |
MH |
|
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Pasquale LR |
|
Pasquale |
Louis R |
LR |
|
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
Kang JH |
|
Kang |
Jae H |
JH |
|
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
Haines JL |
|
Haines |
Jonathan L |
JL |
|
Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. |
Souzeau E |
|
Souzeau |
Emmanuelle |
E |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Zhou T |
|
Zhou |
Tiger |
T |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Siggs OM |
|
Siggs |
Owen M |
OM |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Landers J |
|
Landers |
John |
J |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Awadalla M |
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Awadalla |
Mona |
M |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Sharma S |
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Sharma |
Shiwani |
S |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Mills RA |
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Mills |
Richard A |
RA |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Ridge B |
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Ridge |
Bronwyn |
B |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. |
Lynn D |
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Lynn |
David |
D |
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South Australian Health & Medical Research Institute, School of Medicine, Flinders University, Adelaide, South Australia, Australia. |
Casson R |
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Casson |
Robert |
R |
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South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia. |
Graham SL |
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Graham |
Stuart L |
SL |
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Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia. |
Goldberg I |
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Goldberg |
Ivan |
I |
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Department of Ophthalmology, University of Sydney, Sydney, Australia. |
White A |
|
White |
Andrew |
A |
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Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia. |
Healey PR |
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Healey |
Paul R |
PR |
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Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia. |
Grigg J |
|
Grigg |
John |
J |
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Department of Ophthalmology, University of Sydney, Sydney, Australia. |
Lawlor M |
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Lawlor |
Mitchell |
M |
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Department of Ophthalmology, University of Sydney, Sydney, Australia. |
Mitchell P |
|
Mitchell |
Paul |
P |
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Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia. |
Ruddle J |
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Ruddle |
Jonathan |
J |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
Coote M |
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Coote |
Michael |
M |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
Walland M |
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Walland |
Mark |
M |
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Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. |
Best S |
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Best |
Stephen |
S |
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Department of Ophthalmology, University of Auckland, Auckland, New Zealand. |
Vincent A |
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Vincent |
Andrea |
A |
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Department of Ophthalmology, University of Auckland, Auckland, New Zealand. |
Gale J |
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Gale |
Jesse |
J |
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Department of Ophthalmology, University of Otago, Dunedin, Otago, New Zealand. |
RadfordSmith G |
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RadfordSmith |
Graham |
G |
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School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia. |
Whiteman DC |
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Whiteman |
David C |
DC |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Montgomery GW |
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Montgomery |
Grant W |
GW |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Mackey DA |
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Mackey |
David A |
DA |
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Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia. |
Wiggs JL |
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Wiggs |
Janey L |
JL |
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Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. |
MacGregor S |
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MacGregor |
Stuart |
S |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Craig JE |
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Craig |
Jamie E |
JE |
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Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. jamie.craig@flinders.edu.au. |
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NEIGHBORHOOD consortium |
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INVESTIGATORS |
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LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
Allingham |
R Rand |
RR |
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Brilliant |
Murray |
M |
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Budenz |
Donald L |
DL |
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Fingert |
John H |
JH |
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Gaasterland |
Douglas |
D |
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Gaasterland |
Teresa |
T |
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Hark |
Lisa |
L |
|
Hauser |
Michael |
M |
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Igo |
Robert P |
RP |
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Kraft |
Peter |
P |
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Lee |
Richard K |
RK |
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Lichter |
Paul R |
PR |
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Liu |
Yutao |
Y |
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Moroi |
Syoko |
S |
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Pericak-Vance |
Margaret |
M |
|
Realini |
Anthony |
A |
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Rhee |
Doug |
D |
|
Richards |
Julia E |
JE |
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Ritch |
Robert |
R |
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Schuman |
Joel S |
JS |
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Scott |
William K |
WK |
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Singh |
Kuldev |
K |
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Sit |
Arthur J |
AJ |
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Vollrath |
Douglas |
D |
|
Wollstein |
Gadi |
G |
|
Zack |
Donald J |
DJ |
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JOURNAL |
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VOLUME: 8 |
ISSUE: 1 |
TITLE: Scientific reports |
ISOABBREVIATION: Sci Rep |
YEAR: 2018 |
MONTH: 02 |
DAY: 15 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 2045-2322 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Sci Rep |
COUNTRY: England |
ISSNLINKING: 2045-2322 |
NLMUNIQUEID: 101563288 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
R01 EY022305 |
NEI NIH HHS |
United States |
P30 EY014104 |
NEI NIH HHS |
United States |
R01 CA131332 |
NCI NIH HHS |
United States |
U01 HG004424 |
NHGRI NIH HHS |
United States |
R01 CA136725 |
NCI NIH HHS |
United States |
R21 EY028671 |
NEI NIH HHS |
United States |
UM1 CA167552 |
NCI NIH HHS |
United States |
UM1 CA186107 |
NCI NIH HHS |
United States |
UL1 TR000427 |
NCATS NIH HHS |
United States |
U01 HG004446 |
NHGRI NIH HHS |
United States |
R01 EY023512 |
NEI NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Aged |
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Calcium-Binding Proteins |
genetics |
Case-Control Studies |
genetics |
Endophenotypes |
genetics |
Female |
genetics |
Genetic Predisposition to Disease |
genetics |
Genome-Wide Association Study |
genetics |
Genotype |
genetics |
Glaucoma |
genetics |
Glaucoma, Open-Angle |
metabolism |
Humans |
metabolism |
Intraocular Pressure |
genetics |
LIM Domain Proteins |
genetics |
LIM-Homeodomain Proteins |
genetics |
Male |
genetics |
Membrane Proteins |
genetics |
Middle Aged |
genetics |
Muscle Proteins |
genetics |
Optic Disk |
physiology |
Phenotype |
physiology |
Polymorphism, Single Nucleotide |
genetics |
Retinoic Acid 4-Hydroxylase |
genetics |
Risk Factors |
genetics |
Tonometry, Ocular |
methods |
Transcription Factors |
genetics |
Visual Fields |
genetics |
gamma-Crystallins |
genetics |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
Calcium-Binding Proteins |
0 |
LIM Domain Proteins |
0 |
LIM homeobox transcription factor 1 beta |
0 |
LIM-Homeodomain Proteins |
0 |
LMO7 protein, human |
0 |
MYOF protein, human |
0 |
Membrane Proteins |
0 |
Muscle Proteins |
0 |
Transcription Factors |
0 |
gamma-Crystallins |
148467-57-6 |
CRYGS protein, human |
EC 1.14.14.1 |
CYP26A1 protein, human |
EC 1.14.14.1 |
Retinoic Acid 4-Hydroxylase |
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OTHER ID's |
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