Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

Burdon, Kathryn P., Macgregor, Stuart, Hewitt, Alex W., Sharma, Shiwani, Chidlow, Glyn, Mills, Richard A., Danoy, Patrick, Casson, Robert, Viswanathan, Ananth C., Liu, Jimmy Z., Landers, John, Henders, Anjali K., Wood, John, Souzeau, Emmanuelle, Crawford, April, Leo, Paul, Wang, Jie Jin, Rochtchina, Elena, Nyholt, Dale R., Martin, Nicholas G., Montgomery, Grant W., Mitchell, Paul, Brown, Matthew A., Mackey, David A. and Craig, Jamie E. (2011) Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nature Genetics, 43 6: 574-578. doi:10.1038/ng.824


Author Burdon, Kathryn P.
Macgregor, Stuart
Hewitt, Alex W.
Sharma, Shiwani
Chidlow, Glyn
Mills, Richard A.
Danoy, Patrick
Casson, Robert
Viswanathan, Ananth C.
Liu, Jimmy Z.
Landers, John
Henders, Anjali K.
Wood, John
Souzeau, Emmanuelle
Crawford, April
Leo, Paul
Wang, Jie Jin
Rochtchina, Elena
Nyholt, Dale R.
Martin, Nicholas G.
Montgomery, Grant W.
Mitchell, Paul
Brown, Matthew A.
Mackey, David A.
Craig, Jamie E.
Title Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
Formatted title
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2011-06-01
Year available 2011
Sub-type Article (original research)
DOI 10.1038/ng.824
Open Access Status Not yet assessed
Volume 43
Issue 6
Start page 574
End page 578
Total pages 5
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
Abstract We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.
Formatted abstract
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10−10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10−9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10−14, OR = 1.51, 95% CI 1.35–1.68; rs4977756 combined P = 1.35 × 10−14, OR = 1.39, 95% CI 1.28–1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 535074
241944
FT0991022
Institutional Status UQ
Additional Notes Published under Letter

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
UQ Diamantina Institute Publications
 
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