Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.
| Τίτλος | Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Bailey, J. N. Cooke, Loomis S. J., Kang J. H., R Allingham R., Gharahkhani P., Khor C. Chuen, Burdon K. P., Aschard H., Chasman D. I., Igo R. P., Hysi P. G., Glastonbury C. A., Ashley-Koch A., Brilliant M., Brown A. A., Budenz D. L., Buil A., Cheng C-Y., Choi H., Christen W. G., Curhan G., De Vivo I., Fingert J. H., Foster P. J., Fuchs C., Gaasterland D., Gaasterland T., Hewitt A. W., Hu F., Hunter D. J., Khawaja A. P., Lee R. K., Li Z., Lichter P. R., Mackey D. A., McGuffin P., Mitchell P., Moroi S. E., Perera S. A., Pepper K. W., Qi Q., Realini T., Richards J. E., Ridker P. M., Rimm E., Ritch R., Ritchie M., Schuman J. S., Scott W. K., Singh K., Sit A. J., Song Y. E., Tamimi R. M., Topouzis F., Viswanathan A. C., Verma S. Setia, Vollrath D., Wang J. Jin, Weisschuh N., Wissinger B., Wollstein G., Wong T. Y., Yaspan B. L., Zack D. J., Zhang K., Study E-N. Eye, Weinreb R. N., Pericak-Vance M. A., Small K., Hammond C. J., Aung T., Liu Y., Vithana E. N., MacGregor S., Craig J. E., Kraft P., Howell G., Hauser M. A., Pasquale L. R., Haines J. L., & Wiggs J. L. |
| Corporate Authors | ANZRAG Consortium |
| Journal | Nat Genet |
| Volume | 48 |
| Issue | 2 |
| Pagination | 189-94 |
| Date Published | 2016 Feb |
| ISSN | 1546-1718 |
| Λέξεις κλειδιά | Ataxin-2, Forkhead Transcription Factors, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Polymorphism, Single Nucleotide, Thioredoxin Reductase 2 |
| Abstract | 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. |
| DOI | 10.1038/ng.3482 |
| Alternate Journal | Nat Genet |
| PubMed ID | 26752265 |
| PubMed Central ID | PMC4731307 |
| Grant List | C864/A14136 / / Cancer Research UK / United Kingdom UL1 TR000427 / TR / NCATS NIH HHS / United States R01EY022305 / EY / NEI NIH HHS / United States U01 HG006389 / HG / NHGRI NIH HHS / United States KL2 TR000428 / TR / NCATS NIH HHS / United States G0401527 / / Medical Research Council / United Kingdom R01 EY022305 / EY / NEI NIH HHS / United States R01 EY015473 / EY / NEI NIH HHS / United States UM1 CA182913 / CA / NCI NIH HHS / United States G1000143 / / Medical Research Council / United Kingdom MR/K006584/1 / / Medical Research Council / United Kingdom R01 EY022306 / EY / NEI NIH HHS / United States P30 EY014104 / EY / NEI NIH HHS / United States R01 EY015872 / EY / NEI NIH HHS / United States R01 EY010886 / EY / NEI NIH HHS / United States SRF/01/010 / / Department of Health / United Kingdom / / Wellcome Trust / United Kingdom R01 EY023754 / EY / NEI NIH HHS / United States R01 EY023512 / EY / NEI NIH HHS / United States |
