Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani; Kathryn P. Burdon; Jessica N. Cooke Bailey; Alex W. Hewitt; Matthew H. Law; Louis R. Pasquale; Jae H. Kang; Jonathan L. Haines; Emmanuelle Souzeau; Tiger Zhou; Owen M. Siggs; John Landers; Mona Awadalla; Shiwani Sharma; Richard A. Mills; Bronwyn Ridge; David Lynn; Robert Casson; Stuart L. Graham; Ivan Goldberg; Andrew White; Paul R. Healey; John Grigg; Mitchell Lawlor; Paul Mitchell; Jonathan Ruddle; Michael Coote; Mark Walland; Stephen Best; Andrea Vincent; Jesse Gale; Graham RadfordSmith; David C. Whiteman; Grant W. Montgomery; Nicholas G. Martin; David A. Mackey; Janey L. Wiggs; Stuart MacGregor; Jamie E. Craig; NEIGHBORHOOD Consortium

doi:10.1038/s41598-018-20435-9

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Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

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Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani, Kathryn P. Burdon, Jessica N. Cooke Bailey, Alex W. Hewitt, Matthew H. Law, Louis R. Pasquale, Jae H. Kang, Jonathan L. Haines, Emmanuelle Souzeau, Tiger Zhou, …

Scientific reports, Vol.8(Feb (E-published)), pp.3124-12

15/02/2018

DOI: https://doi.org/10.1038/s41598-018-20435-9

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https://hdl.handle.net/10523/27672

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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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Record Identifier: 9926515080901891
Title: Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma
Creators: Puya Gharahkhani
Kathryn P. Burdon
Jessica N. Cooke Bailey
Alex W. Hewitt
Matthew H. Law
Louis R. Pasquale
Jae H. Kang
Jonathan L. Haines
Emmanuelle Souzeau
Tiger Zhou
Owen M. Siggs
John Landers
Mona Awadalla
Shiwani Sharma
Richard A. Mills
Bronwyn Ridge
David Lynn
Robert Casson
Stuart L. Graham
Ivan Goldberg
Andrew White
Paul R. Healey
John Grigg
Mitchell Lawlor
Paul Mitchell
Jonathan Ruddle
Michael Coote
Mark Walland
Stephen Best
Andrea Vincent
Jesse Gale
Graham RadfordSmith
David C. Whiteman
Grant W. Montgomery
Nicholas G. Martin
David A. Mackey
Janey L. Wiggs
Stuart MacGregor
Jamie E. Craig
NEIGHBORHOOD Consortium
Publication Details: Scientific reports, Vol.8(Feb (E-published)), pp.3124-12
Academic Unit: Surgery and Critical Care (UOW)
Publisher: NATURE PORTFOLIO
Grant note: Cerylid Biosciences (Melbourne) HG005259-01 / National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) CA047988 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) HL043851; HL080467 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Royal Australian UL1TR000427 / NCATS/NIH grant Ramaciotti Establishment Grant NHMRC Medical Genomics Grant; National Health & Medical Research Council (NHMRC) of Australia Donald W. Reynolds Foundation Amgen Alcon Research Institute grant; Novartis Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC); Australian Government; Department of Industry, Innovation and Science; Cooperative Research Centres (CRC) Programme Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS) Queensland Cancer Fund 3R01EY015872-05S1; 3R01EY019126-02S1 / National Eye Institute through ARRA grants New Zealand College of Ophthalmology (RANZCO) Eye Foundation HG004728; U01-HG004424 / GENEVA project R01 CA136725; 5 R01 CA 001833 / US National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) EY015543; EY006827; HL73042; HL073389; EY13315; CA87969; CA49449; UM1 CA186107; UM1 CA167552; EY009149; HG004608; EY008208; EY015473; EY012118; EY015682; EY011671; EY09580; EY013178; RR015574; EY015872; EY010886; EY009847; EY011008; EY144428; EY144448; EY18660 / NIH grants; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1031362; 1037838; 1048037; 1009844; 1031920 / NHMRC; National Health & Medical Research Council (NHMRC) of Australia 535074; 1023911 / National Health and Medical Research Council of Australia; National Health & Medical Research Council (NHMRC) of Australia Fondation Leducq; Leducq Foundation Research to Prevent Blindness; Research to Prevent Blindness (RPB) Allergan; AbbVie BrightFocus Foundation R01EY022305; P30 EY014104 / NIH/NEI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) Harvard Glaucoma Center for Excellence Harvard Medical School Distinguished Scholar award 199600; 552429; 241944; 339462; 389927; 389875; 389891; 389892; 389938; 443036; 442915; 442981; 496610; 496739; 552485; 552498; 1049472; 1050208 / National Health and Medical Research Council (NHMRC) of Australia; National Health & Medical Research Council (NHMRC) of Australia Endometriosis Associations 1RO1EY018246 / National Institutes of Health (NIH) Center for Inherited Research (CIDR) as part of an NIH/National Eye Institute (NEI)
Date published ; e-published: 15/02/2018
Language: English
Resource Type ; Subtype: Journal article