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

Puya Gharahkhani, Kathryn Burdon, Rhys Fogarty, Shiwani Sharma, A W Hewitt, Sarah Martin, Matthew Law, Katie Cremin, Jessica N Cook Bailey, Stephanie Loomis, Louis Pasquale, Jonathan Haines, Michael Hauser, Ananth Viswanathan, Peter McGuffin, Fotis Topouzis, Paul J Foster, Stuart Graham, Robert Casson, Mark ChehadeAndrew J White, Tiger Zhou, Emmanuelle Souzeau, John Landers, Jude Fitzgerald, Sonja Klebe, Jonathan B Ruddle, Ivan Goldberg, Paul Healey, Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD , Richard Mills, Jie Jin Wang, Grant Montgomery, Nicholas Martin, Graham Radford-Smith, David Whiteman, Matthew A Brown, Janey Wiggs, David A Mackey, Paul Mitchell, Stuart Macgregor, Jamie Craig

    Research output: Contribution to journalArticlepeer-review

    130 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 â '19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 â '10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 â '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 pages8
    JournalNature Genetics
    Issue number10
    Publication statusPublished - 31 Aug 2014


    • open-angle glaucoma
    • glaucoma
    • genome-wide association study


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