Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

EPIC-Norfolk Eye Study, David Broadway, Michelle Chan, David Garway-Heath, Shabina Hayat, Nicola Kerrison, Kay-Tee Khaw, Claudia Langenberg, Jian’an Luan, Robert Luben, Robert Scott, Nicholas Wareham, Jennifer Yip, Jing Hua Zhao, ANZRAG Consortium, Shiwani Sharma, Sarah Martin, Tiger Zhou, Emmanuelle Souzeau, John LandersJude Fitzgerald, Richard Mills, Rhys Fogarty, Stuart Graham, Robert Casson, Mark Chehade, Sonja Klebe, Jonathan Ruddle, Ivan Goldberg, Andrew White, Paul Healey, Grant W. Montgomery, Nicholas G. Martin, Graham Radford-Smith, David Whiteman, Matthew H. Law, Matthew Brown, Katie Cremin

    Research output: Contribution to journalArticlepeer-review

    191 Citations (Scopus)


    Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

    Original languageEnglish
    Pages (from-to)189-194
    Number of pages6
    JournalNature Genetics
    Issue number2
    Publication statusPublished - 11 Jan 2016


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