title: Common genetic determinants of intraocular pressure and primary open-angle glaucoma.
abstract: Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
authors.affiliation: Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: Leonieke M E
authors.initials: LM
authors.lastname: van Koolwijk
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Nomdo M
authors.initials: NM
authors.lastname: Jansonius
authors.forename: Francesca
authors.initials: F
authors.lastname: Pasutto
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Janssen
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Ananth C
authors.initials: AC
authors.lastname: Viswanathan
authors.forename: Jacoline B
authors.initials: JB
authors.lastname: ten Brink
authors.forename: S Mohsen
authors.initials: SM
authors.lastname: Hosseini
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.forename: Dominiek D G
authors.initials: DD
authors.lastname: Despriet
authors.forename: Jacqueline J M
authors.initials: JJ
authors.lastname: Willemse-Assink
authors.forename: Rogier
authors.initials: R
authors.lastname: Kramer
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Maksim
authors.initials: M
authors.lastname: Struchalin
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Nicole
authors.initials: N
authors.lastname: Weisschuh
authors.forename: Matthias
authors.initials: M
authors.lastname: Zenkel
authors.forename: Christian Y
authors.initials: CY
authors.lastname: Mardin
authors.forename: Eugen
authors.initials: E
authors.lastname: Gramer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welge-Lüssen
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Francis
authors.initials: F
authors.lastname: Carbonaro
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Céline
authors.initials: C
authors.lastname: Bellenguez
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Foster
authors.forename: Fotis
authors.initials: F
authors.lastname: Topouzis
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.forename: Monika A
authors.initials: MA
authors.lastname: Czudowska
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Roger C W
authors.initials: RC
authors.lastname: Wolfs
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Hans G
authors.initials: HG
authors.lastname: Lemij
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002924:Ciliary Body / Q000378:metabolism / Q000473:pathology; D005260:Female; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D014129:Trabecular Meshwork / Q000378:metabolism / Q000473:pathology
chemical_list: C114909:GAS7 protein, human; D009419:Nerve Tissue Proteins