| Literature DB >> 28073927 |
Henriët Springelkamp1,2, Adriana I Iglesias1,2,3, Aniket Mishra4,5, René Höhn6,7, Robert Wojciechowski8,9,10, Anthony P Khawaja11, Abhishek Nag12, Ya Xing Wang13,14, Jie Jin Wang15, Gabriel Cuellar-Partida4, Jane Gibson16, Jessica N Cooke Bailey17, Eranga N Vithana18,19,20, Puya Gharahkhani4, Thibaud Boutin21, Wishal D Ramdas2, Tanja Zeller22,23, Robert N Luben24, Ekaterina Yonova-Doing12, Ananth C Viswanathan11, Seyhan Yazar25, Angela J Cree26, Jonathan L Haines17, Jia Yu Koh18, Emmanuelle Souzeau27, James F Wilson21,28, Najaf Amin1, Christian Müller22,23, Cristina Venturini12, Lisa S Kearns29, Jae Hee Kang30, Yih Chung Tham18,20, Tiger Zhou27, Elisabeth M van Leeuwen1, Stefan Nickels7, Paul Sanfilippo25,29, Jiemin Liao18,20, Herma van der Linde3, Wanting Zhao18,19, Leonieke M E van Koolwijk1, Li Zheng18,31, Fernando Rivadeneira1,32,33, Mani Baskaran, Sven J van der Lee1, Shamira Perera18,19, Paulus T V M de Jong34,35,36, Ben A Oostra3, André G Uitterlinden1,32,33, Qiao Fan18, Albert Hofman1,33, E-Shyong Tai19,37,38, Johannes R Vingerling2, Xueling Sim38, Roger C W Wolfs2, Yik Ying Teo38,39, Hans G Lemij40, Chiea Chuen Khor18,31,41, Rob Willemsen3, Karl J Lackner42, Tin Aung18,20, Nomdo M Jansonius43, Grant Montgomery44, Philipp S Wild45,46,47, Terri L Young48, Kathryn P Burdon49, Pirro G Hysi12, Louis R Pasquale30,50, Tien Yin Wong18,19,20, Caroline C W Klaver1,2, Alex W Hewitt29,49, Jost B Jonas51, Paul Mitchell15, Andrew J Lotery26, Paul J Foster11, Veronique Vitart21, Norbert Pfeiffer7, Jamie E Craig27, David A Mackey25,49, Christopher J Hammond12, Janey L Wiggs50, Ching-Yu Cheng, Cornelia M van Duijn1, Stuart MacGregor4.
Abstract
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.Entities:
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Year: 2017 PMID： 28073927 PMCID： PMC5968632 DOI： 10.1093/hmg/ddw399
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150