PubMed ID:
22570627
Public Release Type:
Journal
Publication Year: 2012
Affiliation: Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
DOI:
https://doi.org/10.1371/journal.pgen.1002611
Authors:
Amin N,
Aulchenko YS,
Band G,
Barroso I,
Barroso I,
Bellenguez C,
Bellenguez C,
Bergen AA,
Blackburn H,
Blackwell JM,
Blackwell JM,
Bramon E,
Brown MA,
Brown MA,
Bumpstead SJ,
Carbonaro F,
Casas JP,
Corvin A,
Corvin A,
Czudowska MA,
DCCT/EDIC Research Group,
de Jong PT,
Deloukas P,
Deloukas P,
Despriet DD,
Donnelly P,
Donnelly P,
Dronov S,
Duncanson A,
Edkins S,
Foster PJ,
Freeman C,
Giannoulatou E,
Gillman M,
Gramer E,
Gray E,
Gwilliam R,
Hammond CJ,
Hammond N,
Hellenthal G,
Hewitt AW,
Hofman A,
Hosseini SM,
Hunt SE,
Hysi PG,
Ikram MK,
Jankowski J,
Jansonius NM,
Janssen SF,
Jayakumar A,
Klaver CC,
Kramer R,
Langford C,
Lemij HG,
Liddle J,
Macgregor S,
Mackey DA,
Mardin CY,
Markus HS,
Mathew CG,
Mathew CG,
McCann OT,
McCarthy MI,
McGuffin P,
Mitchell P,
Montgomery GW,
Oostra BA,
Palmer CN,
Pasutto F,
Paterson AD,
Pearson R,
Pirinen M,
Plomin R,
Potter SC,
Ramdas WD,
Rautanen A,
Ravindrarajah R,
Reis A,
Ricketts M,
Rivadeneira F,
Sawcer SJ,
Spencer CC,
Spencer CC,
Strange A,
Struchalin M,
Su Z,
ten Brink JB,
Topouzis F,
Trembath RC,
Uitterlinden AG,
van Duijn CM,
van Koolwijk LM,
Vingerling JR,
Viswanathan AC,
Viswanathan AC,
Vukcevic D,
Waller M,
Wang JJ,
Weisschuh N,
Welge-Lüssen U,
Wellcome Trust Case Control Consortium 2,
Weston P,
Whittaker P,
Widaa S,
Willemse-Assink JJ,
Wolfs RC,
Wong TY,
Wood NW,
Young TL,
Zenkel M
Studies:
Diabetes Control and Complications Trial
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.