title: Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1.
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.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Shiwani
authors.initials: S
authors.lastname: Sharma
authors.forename: Glyn
authors.initials: G
authors.lastname: Chidlow
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mills
authors.forename: Patrick
authors.initials: P
authors.lastname: Danoy
authors.forename: Robert
authors.initials: R
authors.lastname: Casson
authors.forename: Ananth C
authors.initials: AC
authors.lastname: Viswanathan
authors.forename: Jimmy Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Landers
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.forename: April
authors.initials: A
authors.lastname: Crawford
authors.forename: Paul
authors.initials: P
authors.lastname: Leo
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Elena
authors.initials: E
authors.lastname: Rochtchina
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D012160:Retina / Q000378:metabolism; D000099179:Myocilin
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C493966:CDKN2B protein, human