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dc.contributor.authorYaspan, Brian L.
dc.contributor.authorHauser, Michael A.
dc.contributor.authorAllingham, R. Rand
dc.contributor.authorOlson, Lana M.
dc.contributor.authorAbdrabou, Wael
dc.contributor.authorBrodeur, Wendy
dc.contributor.authorBudenz, Donald L.
dc.contributor.authorCaprioli, Joseph
dc.contributor.authorCrenshaw, Andrew
dc.contributor.authorCrooks, Kristy
dc.contributor.authorDelBono, Elizabeth
dc.contributor.authorDoheny, Kimberly F.
dc.contributor.authorGaasterland, Douglas
dc.contributor.authorGaasterland, Terry
dc.contributor.authorLaurie, Cathy
dc.contributor.authorLichter, Paul R.
dc.contributor.authorLoomis, Stephanie
dc.contributor.authorLiu, Yutao
dc.contributor.authorMedeiros, Felipe A.
dc.contributor.authorMcCarty, Cathy
dc.contributor.authorMirel, Daniel
dc.contributor.authorMoroi, Sayoko E.
dc.contributor.authorMusch, David C.
dc.contributor.authorRealini, Anthony
dc.contributor.authorRozsa, Frank W.
dc.contributor.authorSchuman, Joel S.
dc.contributor.authorScott, Kathleen
dc.contributor.authorSingh, Kuldev
dc.contributor.authorTrager, Edward H.
dc.contributor.authorVanVeldhuisen, Paul
dc.contributor.authorVollrath, Douglas
dc.contributor.authorWollstein, Gadi
dc.contributor.authorYoneyama, Sachiko
dc.contributor.authorZhang, Kang
dc.contributor.authorWeinreb, Robert N.
dc.contributor.authorErnst, Jason
dc.contributor.authorMasuda, Tomohiro
dc.contributor.authorZack, Don
dc.contributor.authorRichards, Julia E.
dc.contributor.authorPericak-Vance, Margaret
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorWiggs, Janey Lee
dc.contributor.authorKang, Jae Hee Hee
dc.contributor.authorFan, Baojian
dc.contributor.authorWang, Danyi
dc.contributor.authorFriedman, David S.
dc.contributor.authorLee, Richard K.
dc.contributor.authorStein, Joshua D.
dc.contributor.authorKellis, Manolis
dc.contributor.authorPasquale, Louis
dc.date.accessioned2013-03-06T20:47:35Z
dc.date.issued2012
dc.identifier.citationWiggs, Janey L., Brian L. Yaspan, Michael A. Hauser, Jae H. Kang, R. Rand Allingham, Lana M. Olson, Wael Abdrabou, et al. 2012. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genetics 8(4): e1002654.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10370550
dc.description.abstractOptic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10\(^{−18}\)), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10\(^{−11}\)). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10\(^{−12}\)) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10\(^{−10}\)). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002654en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343074/pdf/en_US
dash.licenseLAA
dc.subjectMedicineen_US
dc.subjectOphthalmologyen_US
dc.subjectGlaucomaen_US
dc.subjectInherited Eye Disordersen_US
dc.titleCommon Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucomaen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorWiggs, Janey Lee
dc.date.available2013-03-06T20:47:35Z
dc.identifier.doi10.1371/journal.pgen.1002654*
dash.authorsorderedfalse
dash.contributor.affiliatedWang, Danyi
dash.contributor.affiliatedFan, Baojian
dash.contributor.affiliatedKang, Jae Hee
dash.contributor.affiliatedWiggs, Janey
dash.contributor.affiliatedPasquale, Louis
dash.contributor.affiliatedKellis, Manolis


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