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

Hysi, Pirro G., Cheng, Ching-Yu, Springelkamp, Henriët, Macgregor, Stuart, Bailey, Jessica N. Cooke, Wojciechowski, Robert, Vitart, Veronique, Nag, Abhishek, Hewitt, Alex W., Höhn, René, Venturini, Cristina, Mirshahi, Alireza, Ramdas, Wishal D., Thorleifsson, Gudmar, Vithana, Eranga, Khor, Chiea-Chuen, Stefansson, Arni B, Liao, Jiemin, Haines, Jonathan L., Amin, Najaf, Wang, Ya Xing, Wild, Philipp S., Ozel, Ayse B., Li, Jun Z., Fleck, Brian W., Zeller, Tanja, Staffieri, Sandra E., Teo, Yik-Ying, Cuellar-Partida, Gabriel, Luo, Xiaoyan, Allingham, R Rand, Richards, Julia E., Senft, Andrea, Karssen, Lennart C., Zheng, Yingfeng, Bellenguez, Céline, Xu, Liang, Iglesias, Adriana I., Wilson, James F., Kang, Jae H., van Leeuwen, Elisabeth M., Jonsson, Vesteinn, Thorsteinsdottir, Unnur, Despriet, Dominiek D.G., Ennis, Sarah, Moroi, Sayoko E., Martin, Nicholas G., Jansonius, Nomdo M. and Yazar, Seyhan , BMES GWAS Group, NEIGHBORHOOD Consortium and Wellcome Trust Case Control Consortium 2 (2014) Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nature Genetics, 46 (10), 1126-1130. (doi:10.1038/ng.3087).

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.

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Contributors

Author: Sarah Ennis

Author: Andrew J. Lotery

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