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


ABSTRACT: 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.

SUBMITTER: Gharahkhani P 

PROVIDER: S-EPMC4177327 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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

Gharahkhani Puya P   Burdon Kathryn P KP   Fogarty Rhys R   Sharma Shiwani S   Hewitt Alex W AW   Martin Sarah S   Law Matthew H MH   Cremin Katie K   Bailey Jessica N Cooke JNC   Loomis Stephanie J SJ   Pasquale Louis R LR   Haines Jonathan L JL   Hauser Michael A MA   Viswanathan Ananth C AC   McGuffin Peter P   Topouzis Fotis F   Foster Paul J PJ   Graham Stuart L SL   Casson Robert J RJ   Chehade Mark M   White Andrew J AJ   Zhou Tiger T   Souzeau Emmanuelle E   Landers John J   Fitzgerald Jude T JT   Klebe Sonja S   Ruddle Jonathan B JB   Goldberg Ivan I   Healey Paul R PR   Mills Richard A RA   Wang Jie Jin JJ   Montgomery Grant W GW   Martin Nicholas G NG   RadfordSmith Graham G   Whiteman David C DC   Brown Matthew A MA   Brown Matthew A MA   Wiggs Janey L JL   Mackey David A DA   Mitchell Paul P   MacGregor Stuart S   Craig Jamie E JE  

Nature genetics 20140831 10


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  ...[more]

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