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
29449654
TITLE
Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma.
ABSTRACT
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.
DATE PUBLISHED
2018 02 15
HISTORY
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
AUTHORS
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 Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Zhou T Zhou Tiger T Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Siggs OM Siggs Owen M OM Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Landers J Landers John J Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Awadalla M Awadalla Mona M Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Sharma S Sharma Shiwani S Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Mills RA Mills Richard A RA Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Ridge B Ridge Bronwyn B Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
Lynn D Lynn David D South Australian Health & Medical Research Institute, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
Casson R Casson Robert R South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
Graham SL Graham Stuart L SL Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
Goldberg I Goldberg Ivan I Department of Ophthalmology, University of Sydney, Sydney, Australia.
White A White Andrew A Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
Healey PR Healey Paul R PR Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
Grigg J Grigg John J Department of Ophthalmology, University of Sydney, Sydney, Australia.
Lawlor M Lawlor Mitchell M Department of Ophthalmology, University of Sydney, Sydney, Australia.
Mitchell P Mitchell Paul P Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
Ruddle J Ruddle Jonathan J Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Coote M Coote Michael M Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Walland M Walland Mark M Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Best S Best Stephen S Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
Vincent A Vincent Andrea A Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
Gale J Gale Jesse J Department of Ophthalmology, University of Otago, Dunedin, Otago, New Zealand.
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, Queensland, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Mackey DA Mackey David A DA Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
Wiggs JL Wiggs Janey L JL Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
MacGregor S MacGregor Stuart S QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Craig JE Craig Jamie E JE Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. jamie.craig@flinders.edu.au.
NEIGHBORHOOD consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Allingham R Rand RR
Brilliant Murray M
Budenz Donald L DL
Fingert John H JH
Gaasterland Douglas D
Gaasterland Teresa T
Hark Lisa L
Hauser Michael M
Igo Robert P RP
Kraft Peter P
Lee Richard K RK
Lichter Paul R PR
Liu Yutao Y
Moroi Syoko S
Pericak-Vance Margaret M
Realini Anthony A
Rhee Doug D
Richards Julia E JE
Ritch Robert R
Schuman Joel S JS
Scott William K WK
Singh Kuldev K
Sit Arthur J AJ
Vollrath Douglas D
Wollstein Gadi G
Zack Donald J DJ
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Sci Rep
COUNTRY: England
ISSNLINKING: 2045-2322
NLMUNIQUEID: 101563288
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nat Genet. 2016 Oct;48(10 ):1279-83 27548312
Cites Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2588-96 12766061
Cites Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3509-14 20237253
Cites Annu Rev Nutr. 2011 Aug 21;31:65-87 21529158
Cites Clin Exp Ophthalmol. 2012 May-Jun;40(4):341-9 22356435
Cites Dev Dyn. 2010 Aug;239(8):2161-71 20568247
Cites Bioinformatics. 2010 Jan 1;26(1):139-40 19910308
Cites Nat Commun. 2015 Jan 19;6:5890 25597830
Cites Nat Genet. 2011 Jun;43(6):574-8 21532571
Cites Clin Exp Ophthalmol. 2012 Aug;40(6):569-75 22171965
Cites Br J Ophthalmol. 2006 Mar;90(3):262-7 16488940
Cites Nat Methods. 2011 Dec 04;9(2):179-81 22138821
Cites Nat Genet. 2015 Mar;47(3):291-5 25642630
Cites Science. 2005 Apr 15;308(5720):385-9 15761122
Cites Genome Biol. 2013 Apr 25;14(4):R36 23618408
Cites Nat Genet. 2013 Oct;45(10 ):1238-1243 24013639
Cites Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 22064851
Cites J Allergy Clin Immunol. 2017 Apr;139(4):1148-1157 27554816
Cites Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2613-8 15277484
Cites Nat Genet. 2016 Oct;48(10 ):1284-1287 27571263
Cites BMC Med Genomics. 2009 May 09;2:24 19426536
Cites Bioinformatics. 2009 May 1;25(9):1105-11 19289445
Cites Am J Hum Genet. 2015 Jan 8;96(1):21-36 25500260
Cites Mol Vis. 2011;17 :2072-9 21850183
Cites Ophthalmic Epidemiol. 2011 Oct;18(5):211-6 21961510
Cites Arch Ophthalmol. 1998 Dec;116(12):1640-5 9869795
Cites Invest Ophthalmol Vis Sci. 2011 Mar 28;52(3):1788-92 21398277
Cites Hum Mol Genet. 2017 Jan 15;26(2):438-453 28073927
Cites Hum Mol Genet. 2003 Jun 1;12 (11):1301-12 12761045
Cites Nature. 2012 Sep 6;489(7414):57-74 22955616
Cites Nat Genet. 2014 Oct;46(10 ):1120-1125 25173105
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Gigascience. 2015 Feb 25;4:7 25722852
Cites PLoS Genet. 2012;8(5):e1002611 22570627
Cites Nat Rev Genet. 2010 Jul;11(7):499-511 20517342
Cites Nat Genet. 2013 Mar;45(3):314-8 23396134
Cites Nat Genet. 2015 Nov;47(11):1236-41 26414676
Cites Sci Rep. 2016 Sep 08;6:32894 27604177
Cites Hum Mol Genet. 2015 May 1;24(9):2689-99 25637523
Cites Nat Genet. 2013 Jun;45(6):580-5 23715323
Cites Mol Vis. 2013 Jun 06;19:1238-46 23761726
Cites PLoS Genet. 2014 May 08;10(5):e1004359 24809698
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Sci Rep. 2016 May 31;6:26885 27241461
Cites Nat Genet. 2016 Feb;48(2):189-94 26752265
Cites Genome Res. 2012 Sep;22(9):1790-7 22955989
Cites J Neurobiol. 2006 Jun;66(7):677-86 16688765
Cites Bioinformatics. 2010 Sep 15;26(18):2336-7 20634204
Cites Br J Ophthalmol. 2006 Dec;90(12):1505-9 16825280
Cites J Med Genet. 2005 Sep;42(9):706-10 16141006
Cites Nat Genet. 2010 Oct;42(10):906-9 20835238
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Nat Genet. 2016 Feb;48(2):134-43 26691988
Cites Hum Genomics. 2012 Dec 01;6:26 23199295
Cites BMC Bioinformatics. 2010 Feb 18;11:94 20167110
Cites Nat Genet. 2015 Sep;47(9):1091-8 26258848
Cites Invest Ophthalmol Vis Sci. 2011 May 18;52(6):3436-45 21357400
Cites Nat Struct Mol Biol. 2008 Apr;15(4):373-80 18376416
Cites PLoS Genet. 2012;8(4):e1002654 22570617
Cites EMBO Rep. 2010 Mar;11(3):194-200 20168327
Cites Dev Biol. 2004 Dec 1;276(1):143-57 15531370
Cites Nat Genet. 2013 Nov;45(11):1366-70 24036952
Cites Hum Mol Genet. 2012 Feb 15;21(4):863-73 22072390
GRANTS
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
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
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
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
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
OTHER ID's