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New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics


Springelkamp, H and Iglesias, AI and Mishra, A and Hohn, R and Wojciechowski, R and Khawaja, AP and Nag, A and Wang, YX and Wang, JJ and Cuellar-Partida, G and Gibson, J and Cooke Bailey, JN and Vithana, EN and Gharahkhani, P and Boutin, T and Ramdas, WD and Zeller, T and Luben, RN and Yonova-Doing, E and Viswanathan, AC and Yazar, S and Cree, AJ and Haines, JL and Koh, JY and Souzeau, E and Wilson, JF and Amin, N and Muller, C and Venturini, C and Kearns, LS and Kang, JH and Tham, YC and Zhou, T and van Leeuwen, EM and Nickels, S and Sanfilippo, P and Liao, J and van der Linde, H and Zhao, W and van Koolwijk, LME and Zheng, L and Rivadeneira, F and Baskaran, M and van der Lee, SJ and Perera, S and de Jong, PTVM and Oostra, BA and Uitterlinden, AG and Fan, Q and Hofman, A and Tai, E-S and Vingerling, JR and Sim, X and Wolfs, RCW and Teo, YY and Lemij, HG and Khor, CC and Willemsen, R and Lackner, KJ and Aung, T and Jansonius, NM and Montgomery, G and Wild, PS and Young, TL and Burdon, KP and Hysi, PG and Pasquale, LR and Wong, TY and Klaver, CCW and Hewitt, AW and Jonas, JB and Mitchell, P and Lotery, AJ and Foster, PJ and Vitart, V and Pfeiffer, N and Craig, JE and Mackey, DA and Hammond, CJ and Wiggs, JL and Cheng, C-Y and van Duijn, CM and MacGregor, S, NEIGHBORHOOD Consortium, New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics, Human Molecular Genetics, 26, (2) pp. 438-453. ISSN 0964-6906 (2017) [Refereed Article]

Copyright Statement

Copyright The Author 2017. Published by Oxford University Press. All rights reserved.

DOI: doi:10.1093/hmg/ddw399


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:117060
Year Published:2017
Web of Science® Times Cited:98
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-05-30
Last Modified:2022-08-25

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