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PMID: 21532571 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 43 ·No. 6 ·2011-06-00 ·Pages 574-8

Burdon KP, Macgregor S, Hewitt AW, Sharma S, Chidlow G, Mills RA, Danoy P, Casson R, Viswanathan AC, Liu JZ, Landers J, Henders AK, Wood J, Souzeau E, Crawford A, Leo P, Wang JJ, Rochtchina E, Nyholt DR, Martin NG, Montgomery GW, Mitchell P, Brown MA, Mackey DA, Craig JE

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.

MeSH Terms
Aged Aged, 80 and over Animals Cyclin-Dependent Kinase Inhibitor p15/genetics Cytoskeletal Proteins/genetics Eye Proteins/genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Glaucoma, Open-Angle/genetics Glycoproteins/genetics Humans Male Polymorphism, Single Nucleotide Rats Retina/metabolism
Chemicals
CDKN2B protein, human Cyclin-Dependent Kinase Inhibitor p15 Cytoskeletal Proteins Eye Proteins Glycoproteins trabecular meshwork-induced glucocorticoid response protein
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Burdon Kathryn P
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
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
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.824
Published
2011-06-00
Epub
2011-00-01
Pages
574-8
Language
English
Region
United States
NLM ID
9216904
Subset
IM
Grants
PHS HHS · 2007-2010 · United States
External Links
PubMed source DOI: 10.1038/ng.824 View journal details
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