Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
| Τίτλος | Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Gharahkhani, P., Burdon K. P., Fogarty R., Sharma S., Hewitt A. W., Martin S., Law M. H., Cremin K., Bailey J. N. Cooke, Loomis S. J., Pasquale L. R., Haines J. L., Hauser M. A., Viswanathan A. C., McGuffin P., Topouzis F., Foster P. J., Graham S. L., Casson R. J., Chehade M., White A. J., Zhou T., Souzeau E., Landers J., Fitzgerald J. T., Klebe S., Ruddle J. B., Goldberg I., Healey P. R., Mills R. A., Wang J. Jin, Montgomery G. W., Martin N. G., RadfordSmith G., Whiteman D. C., Brown M. A., Wiggs J. L., Mackey D. A., Mitchell P., MacGregor S., & Craig J. E. |
| Corporate Authors | Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD consortium |
| Journal | Nat Genet |
| Volume | 46 |
| Issue | 10 |
| Pagination | 1120-1125 |
| Date Published | 2014 Oct |
| ISSN | 1546-1718 |
| Λέξεις κλειδιά | Aged, Aged, 80 and over, ATP Binding Cassette Transporter 1, Australia, Cohort Studies, Female, Gene Expression, Gene Frequency, Genetic Predisposition to Disease, Genotype, Glaucoma, Open-Angle, Humans, Hydro-Lyases, Immunoblotting, Male, Meta-Analysis as Topic, Microfilament Proteins, Middle Aged, Polymorphism, Single Nucleotide, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, United States |
| 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. |
| DOI | 10.1038/ng.3079 |
| Alternate Journal | Nat Genet |
| PubMed ID | 25173105 |
| PubMed Central ID | PMC4177327 |
| Grant List | U01 HG004728 / HG / NHGRI NIH HHS / United States R01 CA001833 / CA / NCI NIH HHS / United States G1000143 / / Medical Research Council / United Kingdom R01 CA136725 / CA / NCI NIH HHS / United States G0401527 / / Medical Research Council / United Kingdom R01 EY022305 / EY / NEI NIH HHS / United States 084620 / / Wellcome Trust / United Kingdom R01 EY015473 / EY / NEI NIH HHS / United States MR/K006584/1 / / Medical Research Council / United Kingdom P30 EY014104 / EY / NEI NIH HHS / United States R01 EY023512 / EY / NEI NIH HHS / United States |
