New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.
View/ Open
Date
2017-01Author
Springelkamp, Henriët
Iglesias, Adriana
Mishra, Aniket
Hohn, Rene
Wojciechowski, Robert
Khwaja, Anthony P
Nag, Abhishek
Wang, Ya Xing
Wang, Jie Jin
Cuellar-Partida, Gabriel
Gibson, Jane
Cooke-Bailey, Jessica N
Vithana, Eranga
Gharahkhani, Puya
Boutin, Thibaud
Ramdas, Wishal D
Zeller, Tanja
Luben, Robert N
Yonova-Doing, Ekaterina
Yazar, Seyhan
Cree, Angela J
Haines, Jonathan L
Koh, Jia Yu
Souzeau, Emmanuelle
Wilson, James F
Amin, Najaf
Muller, Christian
Venturini, Cristina
Kearns, Lisa S
Kang, Jae Hee
Tham, Yih Chung
Zhou, Tiger
van Leeuwen, Elisabeth M
NIckels, Stefan
Sanfilippo, Paul Gerard
Liao, Jiemin
van der Linde, Herma
Zhao, Wanting
van Koolwijk, Leonieke M E
Zheng, Li
Rivadeneira, Fernando
Baskaran, Mani
van der Lee, Sven J
Perera, Shamira
de Jong, Paulus T V M
Oostra, Ben A
Uitterlinden, Andre G
Fan, Qiao
Hofman, Albert
Tai, E-Shyong
Vingerling, Johannes R
Sim, Xueling
Wolfs, Roger C W
Teo, Yik Ying
Lemij, Hans G
Khor, Chiea Chuen
Willemsen, Rob
Lackner, Karl J
Aung, Tin
Jansonius, Nomdo M
Montgomery, Grant W
Wild, Philipp S
Young, Terri L
Burdon, Kathryn Penelope
Hysi, Pirro G
Pasquale, Louis R
Wong, Tien Yin
Klaver, Caroline C W
Hewitt, Alex W
Jonas, Jost B
Mitchell, Paul
Lotery, Andrew J
Foster, Paul J
Vitart, Veronique
Pfeiffer, Norbert
Craig, Jamie E
Mackey, David A
Hammond, Christopher J
Wiggs, Janey L
Cheng, Ching-Yu
van Duijin, Cornelia M
MacGregor, Stuart
Viswanathan, Ananth C
Metadata
Show full item recordAbstract
Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase 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.
Description
Pre-copyedited author-produced manuscript made available following 12 month embargo from date of publication in accordance with publisher copyright policy.