Journal Article

Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Loomis, Stephanie J, Spector, Timothy D, Thorleifsson, Gudmar, Stefansson, Arni B, Vingerling, Johannes R, Young, Terri L, Li, Jun Z, Xu, Liang, Nag, Abhishek, Pennell, Craig E, Amin, Najaf, Jonasson, Fridbert, Mackey, David A, Bailey, Jessica N Cooke, Hewitt, Alex W, Rivadeneira, Fernando, Khor, Chiea-Chuen, Pasquale, Louis R, Cuellar-Partida, Gabriel, Cheng, Ching-Yu, Hauser, Michael A, Höhn, René, Stefansson, Kari, Richards, Julia E, Leo, Paul, Wojciechowski, Robert, Pfeiffer, Norbert, Luo, Xiaoyan, Ennis, Sarah, van Koolwijk, Leonieke M.E., Springelkamp, Henriët, Mirshahi, Alireza, Tai, E-Shyong, Haines, Jonathan L, Hammond, Christopher J, Wilson, James F, van Leeuwen, Elisabeth M, Moroi, Sayoko E, Jansonius, Nomdo M, Burdon, Kathryn P, Uitterlinden, André G, Wang, Ya Xing, Fleck, Brian W, Hofman, Albert, Craig, Jamie E, Viswanathan, Ananth, Senft, Andrea, Despriet, Dominiek D.G., Oostra, Ben A, Macgregor, Stuart, Small, Kerrin S, Thorsteinsdottir, Unnur, Wolfs, Roger C.W., Wong, Tien-Yin, Allingham, R Rand, Kang, Jae H, Jonsson, Vesteinn, Zeller, Tanja, Maubaret, Cécilia, Vitart, Veronique, Staffie

2014

Overview

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and IOP variability may herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multiethnic participants for IOP. We confirm genetic association of known loci for IOP and primary open angle glaucoma (POAG) and identify four new IOP loci located on chromosome 3q25.31 within the FNDC3B gene (p=4.19×10−08 for rs6445055), two on chromosome 9 (p=2.80×10−11 for rs2472493 near ABCA1 and p=6.39×10−11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best p=1.04×10−11 for rs747782). Separate meta-analyses of four independent POAG cohorts, totaling 4,284 cases and 95,560 controls, show that three of these IOP loci are also associated with POAG.