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dc.contributor.authorRamdas, Wishal D
dc.contributor.authorvan Koolwijk, Leonieke M E
dc.contributor.authorLemij, Hans G
dc.contributor.authorPasutto, Francesca
dc.contributor.authorCree, Angela J
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorJanssen, Sarah F
dc.contributor.authorJacoline, Ten Brink
dc.contributor.authorAmin, Najaf
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorWolfs, Roger C W
dc.contributor.authorWalters, G Bragi
dc.contributor.authorJonasson, Fridbert
dc.contributor.authorWeisschuh, Nicole
dc.contributor.authorMardin, Christian Y
dc.contributor.authorGibson, Jane
dc.contributor.authorZegers, Richard H C
dc.contributor.authorHofman, Albert
dc.contributor.authorde Jong, Paulus T V M
dc.contributor.authorUitterlinden, André G
dc.contributor.authorOostra, Ben A
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorGramer, Eugen
dc.contributor.authorWelgen-Lüssen, Ulrich C
dc.contributor.authorKirwan, James F
dc.contributor.authorBergen, Arthur A B
dc.contributor.authorReis, André
dc.contributor.authorStefansson, Kari
dc.contributor.authorLotery, Andrew J
dc.contributor.authorVingerling, Johannes R
dc.contributor.authorJansonius, Nomdo M
dc.contributor.authorKlaver, Caroline C W
dc.contributor.authorvan Duijn, Cornelia M
dc.date.accessioned2012-06-08T09:35:04Z
dc.date.available2012-06-08T09:35:04Z
dc.date.issued2011-06-15
dc.date.submitted2012-06-08
dc.identifier.citationCommon genetic variants associated with open-angle glaucoma. 2011, 20 (12):2464-71 Hum. Mol. Genet.en_GB
dc.identifier.issn1460-2083
dc.identifier.pmid21427129
dc.identifier.doi10.1093/hmg/ddr120
dc.identifier.urihttp://hdl.handle.net/2336/228031
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractOpen-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.
dc.description.sponsorshipErasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam Netherlands Organization of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 RIDE2 Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Center for Medical Systems Biology (CMSB) of NGI Netherlands Organization for Health Research and Development (ZonMw) 2200.0035 Lijf en Leven, Krimpen a/d Lek MD Fonds, Utrecht EUROSPAN (European Special Populations Research Network), European Commission 018947 (LSHG-CT-2006-01947) International Glaucoma Association UK and Eire Glaucoma Society Optegra UK Ltd.en_GB
dc.language.isoenen
dc.publisherOxford University Pressen_GB
dc.relation.urlhttp://dx.doi.org/10.1093/hmg/ddr120en_GB
dc.rightsArchived with thanks to Human molecular geneticsen_GB
dc.subject.meshBasic Helix-Loop-Helix Transcription Factorsen_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshCyclin-Dependent Kinase Inhibitor p15en_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshGlaucoma, Open-Angleen_GB
dc.subject.meshHomeodomain Proteinsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLogistic Modelsen_GB
dc.subject.meshOdds Ratioen_GB
dc.subject.meshOptic Disken_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.titleCommon genetic variants associated with open-angle glaucoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.en_GB
dc.identifier.journalHuman molecular geneticsen_GB
html.description.abstractOpen-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.


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