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, 46 (10), 1126-1130

Genome-wide Analysis of Multi-Ancestry Cohorts Identifies New Loci Influencing Intraocular Pressure and Susceptibility to Glaucoma

Pirro G Hysi #  1 Ching-Yu Cheng #  2   3   4   5 Henriët Springelkamp #  6   7 Stuart Macgregor #  8 Jessica N Cooke Bailey #  9 Robert Wojciechowski #  10   11 Veronique Vitart  12 Abhishek Nag  1 Alex W Hewitt  13 René Höhn  14 Cristina Venturini  1   15 Alireza Mirshahi  14 Wishal D Ramdas  6   7 Gudmar Thorleifsson  16 Eranga Vithana  2   3   5 Chiea-Chuen Khor  3   17 Arni B Stefansson  18 Jiemin Liao  2   3 Jonathan L Haines  9 Najaf Amin  7 Ya Xing Wang  19 Philipp S Wild  20 Ayse B Ozel  21 Jun Z Li  21 Brian W Fleck  22 Tanja Zeller  23 Sandra E Staffieri  13 Yik-Ying Teo  4   24 Gabriel Cuellar-Partida  8 Xiaoyan Luo  25 R Rand Allingham  26 Julia E Richards  6 Andrea Senft  27 Lennart C Karssen  7 Yingfeng Zheng  2   4 Céline Bellenguez  28   29   30 Liang Xu  19 Adriana I Iglesias  7 James F Wilson  31 Jae H Kang  32 Elisabeth M van Leeuwen  7 Vesteinn Jonsson  33 Unnur Thorsteinsdottir  16 Dominiek D G Despriet  6 Sarah Ennis  34 Sayoko E Moroi  35 Nicholas G Martin  36 Nomdo M Jansonius  37 Seyhan Yazar  38 E-Shyong Tai  4   5   39 Philippe Amouyel  27   28   29   40 James Kirwan  41 Leonieke M E van Koolwijk  7 Michael A Hauser  26   42 Fridbert Jonasson  43 Paul Leo  44 Stephanie J Loomis  45 Rhys Fogarty  46 Fernando Rivadeneira  7   47   48 Lisa Kearns  13 Karl J Lackner  49 Paulus T V M de Jong  50   51   52 Claire L Simpson  11 Craig E Pennell  53 Ben A Oostra  54 André G Uitterlinden  7   47   48 Seang-Mei Saw  2   3   4   5 Andrew J Lotery  55 Joan E Bailey-Wilson  11 Albert Hofman  7   48 Johannes R Vingerling  6   7 Cécilia Maubaret  56   57 Norbert Pfeiffer  14 Roger C W Wolfs  6 Hans G Lemij  58 Terri L Young  25 Louis R Pasquale  32   45 Cécile Delcourt  56   57 Timothy D Spector  1 Caroline C W Klaver  6   7 Kerrin S Small  1 Kathryn P Burdon  46 Kari Stefansson  16 Tien-Yin Wong  2   3   4 BMES GWAS GroupNEIGHBORHOOD ConsortiumWellcome Trust Case Control Consortium 2Ananth Viswanathan  59 David A Mackey  13   38 Jamie E Craig  46 Janey L Wiggs  45 Cornelia M van Duijn  7 Christopher J Hammond  1 Tin Aung  2   3
Affiliations

Genome-wide Analysis of Multi-Ancestry Cohorts Identifies New Loci Influencing Intraocular Pressure and Susceptibility to Glaucoma

Pirro G Hysi et al. Nat Genet.

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.

Figures

Figure 1
Figure 1. Flowchart of the analyses
Results from a meta-analysis of IOP in participants from 18 general population cohorts were validated in four clinical case control cohorts and checked for transcription regulation activity in three tissues from 856 British subjects.
Figure 2
Figure 2. Manhattan plots of the results from the meta-analyses of results from 18 multi-ethnic cohorts from the IGGC
The 22 autosomes are plotted along the x-axis, whereas the values in the y-axis denote the −log10 -transformed p-values from the meta-analysis of association with IOP observed for any of the SNPs. Loci previously associated with IOP or glaucoma have been grayed out.

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