Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

Puya Gharahkhani*, Kathryn P. Burdon, Rhys Fogarty, Shiwani Sharma, Alex W. Hewitt, Sarah Martin, Matthew H. Law, Katie Cremin, Jessica N Cooke Bailey, Stephanie J. Loomis, Louis R. Pasquale, Jonathan L. Haines, Michael A. Hauser, Ananth C. Viswanathan, Peter McGuffin, Fotis Topouzis, Paul J. Foster, Stuart L. Graham, Robert J. Casson, Mark ChehadeAndrew J. White, Tiger Zhou, Emmanuelle Souzeau, John Landers, Jude T. Fitzgerald, Sonja Klebe, Jonathan B. Ruddle, Ivan Goldberg, Paul R. Healey, Richard A. Mills, Jie Jin Wang, Grant W. Montgomery, Nicholas G. Martin, Graham Radford-Smith, David C. Whiteman, Matthew A. Brown, Janey L. Wiggs, David A. Mackey, Paul Mitchell, Stuart Macgregor, Jamie E. Craig

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    128 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)1120-1125
    Number of pages6
    JournalNature Genetics
    Issue number10
    Publication statusPublished - 26 Sep 2014


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