학술논문
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1.
Document Type
Article
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; Jie Jin Wang; Rochtchina, Elena; Nyholt, Dale R.; Martin, Nicholas G.
Source
Subject
*DISEASE susceptibility
*GLAUCOMA
*GENOMICS
*LABORATORY rats
*BLINDNESS
*LOCUS (Genetics)
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Language
ISSN
1061-4036
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. [ABSTRACT FROM AUTHOR]