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Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Version 2 2024-10-28, 04:12
Version 1 2023-05-21, 13:05
journal contribution
posted on 2024-10-28, 04:12 authored by P Gharahkhani, E Jorgenson, P Hysi, AP Khawaja, S Pendergrass, X Han, JS Ong, Alexander HewittAlexander Hewitt, AV Segre, JM Rouhana, AR Hamel, RP Igo, H Choquet, A Qassim, NS Josyula, JN Cooke Bailey, PWM Bonnemaijer, A Iglesias, OM Siggs, TL Young, V Vitart, AAHJ Thiadens, J Karjalainen, S Uebe, RB Melles, KS Nair, R Luben, M Simcoe, N Amersinghe, AJ Cree, R Hohn, A Poplawski, LJ Chen, SS Rong, T Aung, EN Vithana, G Tamiya, Y Shiga, M Yamamoto, T Nakazawa, H Currant, X Wang, A Auton, MK Lupton, NG Martin, A Ashaye, O Olawoye, SE Williams, S Akato, M Ramsay, K Hashimoto, Y Kamatani, M Akiyama, Y Momozawa, PJ Foster, PT Khaw, JE Morgan, NG Strouthidis, P Kraft, JH Hang, CP Pang, F Pasutto, P Mitchell, AJ Lotery, LR Pasquale, CCW Klaver, M Hauser, CC Khor, DA Mackey, M Kubo, CY Cheng, JE Craig, S MacGregor, JL Wiggs
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

History

Publication title

Nature Communications

Volume

12

Issue

1

Article number

1258

Number

1258

Pagination

1-16

ISSN

2041-1723

Department/School

Menzies Institute for Medical Research, Integrated Marine Observing System

Publisher

Nature

Publication status

  • Published

Place of publication

London

Socio-economic Objectives

200101 Diagnosis of human diseases and conditions, 200104 Prevention of human diseases and conditions, 200105 Treatment of human diseases and conditions