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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gharahkhani, P; Burdon, KP; Fogarty, R; Sharma, S; Hewitt, AW; Martin, S; Law, MH; Cremin, K; Bailey, JNC; Loomis, SJ; Pasquale, LR; Haines, JL; Hauser, MA; Viswanathan, AC; McGuffin, P; Topouzis, F; Foster, PJ; Graham, SL; Casson, RJ; Chehade, M; White, AJ; Zhou, T; Souzeau, E; Landers, J; Fitzgerald, JT; Klebe, S; Ruddle, JB; Goldberg, I; Healey, PR; Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD consortium, ; Mills, RA; Wang, JJ; Montgomery, GW; Martin, NG; RadfordSmith, G; Whiteman, DC; Brown, MA; Wiggs, JL; Mackey, DA; Mitchell, P; MacGregor, S; Craig, JE

Published Date

  • October 2014

Published In

Volume / Issue

  • 46 / 10

Start / End Page

  • 1120 - 1125

PubMed ID

  • 25173105

Pubmed Central ID

  • 25173105

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.3079


  • eng

Conference Location

  • United States