1. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
- Author
-
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, Mills RA, Wang JJ, Montgomery GW, Martin NG, RadfordSmith G, Whiteman DC, Brown MA, Wiggs JL, Mackey DA, Mitchell P, MacGregor S, and Craig JE
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Aged, Aged, 80 and over, Australia, Cohort Studies, Female, Gene Expression, Gene Frequency, Genotype, Glaucoma, Open-Angle metabolism, Humans, Immunoblotting, Male, Meta-Analysis as Topic, Microfilament Proteins metabolism, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, United States, ATP Binding Cassette Transporter 1 genetics, Genetic Predisposition to Disease genetics, Glaucoma, Open-Angle genetics, Hydro-Lyases genetics, Microfilament Proteins genetics, Polymorphism, Single Nucleotide
- 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.
- Published
- 2014
- Full Text
- View/download PDF