Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.
Hysi PG., Cheng C-Y., Springelkamp H., Macgregor S., Bailey JNC., Wojciechowski R., Vitart V., Nag A., Hewitt AW., Höhn R., Venturini C., Mirshahi A., Ramdas WD., Thorleifsson G., Vithana E., Khor C-C., Stefansson AB., Liao J., Haines JL., Amin N., Wang YX., Wild PS., Ozel AB., Li JZ., Fleck BW., Zeller T., Staffieri SE., Teo Y-Y., Cuellar-Partida G., Luo X., Allingham RR., Richards JE., Senft A., Karssen LC., Zheng Y., Bellenguez C., Xu L., Iglesias AI., Wilson JF., Kang JH., van Leeuwen EM., Jonsson V., Thorsteinsdottir U., Despriet DDG., Ennis S., Moroi SE., Martin NG., Jansonius NM., Yazar S., Tai E-S., Amouyel P., Kirwan J., van Koolwijk LME., Hauser MA., Jonasson F., Leo P., Loomis SJ., Fogarty R., Rivadeneira F., Kearns L., Lackner KJ., de Jong PTVM., Simpson CL., Pennell CE., Oostra BA., Uitterlinden AG., Saw S-M., Lotery AJ., Bailey-Wilson JE., Hofman A., Vingerling JR., Maubaret C., Pfeiffer N., Wolfs RCW., Lemij HG., Young TL., Pasquale LR., Delcourt C., Spector TD., Klaver CCW., Small KS., Burdon KP., Stefansson K., Wong T-Y., BMES GWAS Group None., NEIGHBORHOOD Consortium None., Wellcome Trust Case Control Consortium 2 None., Viswanathan A., Mackey DA., Craig JE., Wiggs JL., van Duijn CM., Hammond CJ., Aung T.
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might 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 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) 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 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.