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

Hysi PG1, Cheng CY2, Springelkamp H3, Macgregor S4, Bailey JN5, Wojciechowski R6, Vitart V7, Nag A8, Hewitt AW9, Höhn R10, Venturini C11, Mirshahi A10,Ramdas WD12, Thorleifsson G13, Vithana E14, Khor CC15, Stefansson AB16, Liao J17, Haines JL18, Amin N19, Wang YX20, Wild PS21, Ozel AB22, Li JZ22,Fleck BW23, Zeller T24, Staffieri SE9, Teo YY25, Cuellar-Partida G26, Luo X27, Allingham RR28, Richards JE29, Senft A30, Karssen LC19, Zheng Y31,Bellenguez C32, Xu L20, Iglesias AI19, Wilson JF33, Kang JH34, van Leeuwen EM19, Jonsson V35, Thorsteinsdottir U13, Despriet DD29, Ennis S36, Moroi SE37,Martin NG38, Jansonius NM39, Yazar S40, Tai ES41, Amouyel P42, Kirwan J43, van Koolwijk LM19, Hauser MA44, Jonasson F45, Leo P46, Loomis SJ47, Fogarty R48, Rivadeneira F49, Kearns L9, Lackner KJ50, de Jong PT51, Simpson CL52, Pennell CE53, Oostra BA54, Uitterlinden AG49, Saw SM55, Lotery AJ56, Bailey-Wilson JE52, Hofman A57, Vingerling JR12, Maubaret C58, Pfeiffer N10, Wolfs RC29, Lemij HG59, Young TL27, Pasquale LR60, Delcourt C58, Spector TD8,Klaver CC12, Small KS8, Burdon KP48, Stefansson K13, Wong TY61; BMES GWAS Group; NEIGHBORHOOD Consortium; Wellcome Trust Case Control Consortium 2, Viswanathan A62, Mackey DA63, Craig JE64, Wiggs JL65, van Duijn CM66, Hammond CJ1, Aung T67.

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Abstract

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.