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

Springelkamp, Henriet, Iglesias, Adriana I., Mishra, Aniket, Hoehn, Rene, Wojciechowski, Robert, Khawaja, Anthony P., Nag, Abhishek, Wang, Ya Xing, Wang, Jie Jin, Cuellar-Partida, Gabriel, Gibson, Jane, Bailey, Jessica N. Cooke, Vithana, Eranga N., Gharahkhani, Puya, Boutin, Thibaud, Ramdas, Wishal D., Zeller, Tanja, Luben, Robert N., Yonova-Doing, Ekaterina, Viswanathan, Ananth C., Yazar, Seyhan, Cree, Angela J., Haines, Jonathan L., Koh, Jia Yu, Souzeau, Emmanuelle, Wilson, James F., Amin, Najaf, Mueller, Christian, Venturini, Cristina, Kearns, Lisa S., Kang, Jae Hee, Tham, Yih Chung, Zhou, Tiger, van Leeuwen, Elisabeth M., Nickels, Stefan, Sanfilippo, Paul, 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, Wild, Philipp S., Young, Terri L., Burdon, Kathryn P., 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 Duijn, Cornelia M. and MacGregor, Stuart (2017) 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: 438-453. doi:10.1093/hmg/ddw399

Author Springelkamp, Henriet
Iglesias, Adriana I.
Mishra, Aniket
Hoehn, Rene
Wojciechowski, Robert
Khawaja, Anthony P.
Nag, Abhishek
Wang, Ya Xing
Wang, Jie Jin
Cuellar-Partida, Gabriel
Gibson, Jane
Bailey, Jessica N. Cooke
Vithana, Eranga N.
Gharahkhani, Puya
Boutin, Thibaud
Ramdas, Wishal D.
Zeller, Tanja
Luben, Robert N.
Yonova-Doing, Ekaterina
Viswanathan, Ananth C.
Yazar, Seyhan
Cree, Angela J.
Haines, Jonathan L.
Koh, Jia Yu
Souzeau, Emmanuelle
Wilson, James F.
Amin, Najaf
Mueller, Christian
Venturini, Cristina
Kearns, Lisa S.
Kang, Jae Hee
Tham, Yih Chung
Zhou, Tiger
van Leeuwen, Elisabeth M.
Nickels, Stefan
Sanfilippo, Paul
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
Wild, Philipp S.
Young, Terri L.
Burdon, Kathryn P.
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 Duijn, Cornelia M.
MacGregor, Stuart
Title New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2017-01-15
Year available 2017
Sub-type Article (original research)
DOI 10.1093/hmg/ddw399
Open Access Status Not yet assessed
Volume 26
Issue 2
Start page 438
End page 453
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted 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.
Keyword Genome-wide association
Population-based epidemiology
Susceptibility loci
Common variants
Identifies 5
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 19 Apr 2017, 16:55:56 EST by Gabriel Cuellar Partida on behalf of School of Medicine