6533b7d2fe1ef96bd125f585
RESEARCH PRODUCT
New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics
Louis R. PasqualeLouis R. PasqualeJia Yu KohAniket MishraAniket MishraAnanth C. ViswanathanMani BaskaranJie Jin WangJonathan L. HainesAngela J. CreeHenriët SpringelkampPuya GharahkhaniSeyhan YazarGabriel Cuellar-partidaHerma C. Van Der LindeHans G LemijThibaud BoutinYik Ying TeoStuart MacgregorJae H. KangLi ZhengLeonieke M E Van KoolwijkJaney L. WiggsQiao FanCornelia M. Van DuijnRob WillemsenRené HöhnStefan NickelsTien Yin WongNajaf AminShamira A. PereraLisa S. KearnsPirro G. HysiRoger C. W. WolfsJost B. JonasRobert LubenTiger ZhouAndré G. UitterlindenWanting ZhaoElisabeth M. Van LeeuwenWishal D. RamdasCristina VenturiniCaroline C W KlaverXueling SimSven J. Van Der LeeTin AungJiemin LiaoKarl J. LacknerAndrew J. LoteryAdriana I IglesiasAlbert HofmanBen A. OostraFernando RivadeneiraPaul J. FosterEranga N. VithanaNomdo M. JansoniusJamie E CraigE. Shyong TaiVeronique VitartChing-yu ChengEkaterina Yonova-doingRobert WojciechowskiChiea Chuen KhorKathryn P. BurdonAnthony P KhawajaChristopher J HammondJane GibsonNorbert PfeifferTanja ZellerJohannes R. VingerlingEmmanuelle SouzeauYa Xing WangGrant W. MontgomeryDavid A. MackeyDavid A. MackeyPhilipp S. WildPaul MitchellTerri L. YoungAlex W. HewittAlex W. HewittPaulus T. V. M. De JongPaul G. SanfilippoPaul G. SanfilippoAbhishek NagYih Chung ThamChristian P. MüllerJessica N. Cooke BaileyJames F. Wilsonsubject
0301 basic medicineMaleIntraocular pressuregenetic structuresOptic diskGlaucomaPROTEINGenome-wide association studyIDENTIFIES 5Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Optic neuropathyOptic Nerve DiseasesPROSTATEGenetics (clinical)RISKAssociation Studies ArticlesCOMMON VARIANTSGeneral MedicineMiddle AgedCANCER3. Good healthmedicine.anatomical_structureOptic nerveFemaleGlaucoma Open-AngleOptic discCyclin-Dependent Kinase Inhibitor p21medicine.medical_specialtyOpen angle glaucomaSUSCEPTIBILITY LOCIOptic Disk610 Medicine & healthBiology03 medical and health sciencesTonometry OcularOphthalmologyGeneticsmedicineHumansGENOME-WIDE ASSOCIATIONMolecular BiologyIntraocular PressureHomeodomain ProteinsP53Genome HumanPOPULATION-BASED EPIDEMIOLOGYZebrafish Proteinsmedicine.diseaseeye diseases030104 developmental biologysense organsGenome-Wide Association Studydescription
Item does not contain fulltext Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-15 | Human Molecular Genetics |