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 GoldbergAndrew 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, The NEIGHBORHOOD consortium

*Corresponding author for this work

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    31 Citations (Scopus)
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    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.

    Original languageEnglish
    Article number3124
    Pages (from-to)1-12
    Number of pages12
    JournalScientific Reports
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2018

    Bibliographical note

    Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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