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

Title: Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Authors: Gharahkhani, P; https://orcid.org/orcid:0000-0002-4203-5952; Jorgenson, E; https://orcid.org/orcid:0000-0002-5829-8191; Hysi, P; https://orcid.org/orcid:0000-0001-5752-2510; Khawaja, AP; https://orcid.org/orcid:0000-0001-6802-8585; Pendergrass, S; https://orcid.org/orcid:0000-0002-0565-6522; Han, X; https://orcid.org/orcid:0000-0002-3823-7308; Ong, JS; https://orcid.org/orcid:0000-0002-6062-710X; Hewitt, AW; https://orcid.org/orcid:0000-0002-5123-5999; Segrè, AV; https://orcid.org/orcid:0000-0001-6806-5845; Rouhana, JM; https://orcid.org/orcid:0000-0002-8599-0271; Hamel, AR; https://orcid.org/orcid:0000-0001-6420-9573; Igo, RP; https://orcid.org/orcid:0000-0002-0024-1993; Choquet, H; https://orcid.org/orcid:0000-0001-9839-8667; Qassim, A; https://orcid.org/orcid:0000-0002-2911-2941; Josyula, NS; https://orcid.org/orcid:0000-0003-2782-8812; Bailey, JNC; https://orcid.org/orcid:0000-0002-4001-8702; Bonnemaijer, PWM; https://orcid.org/orcid:0000-0001-5154-6765; Iglesias, A; https://orcid.org/orcid:0000-0001-5532-764X; Siggs, OM; https://orcid.org/orcid:0000-0003-2840-4851; Young, TL; https://orcid.org/orcid:0000-0001-6994-9941; Vitart, V; https://orcid.org/orcid:0000-0002-4991-3797; Thiadens, AAHJ; https://orcid.org/orcid:0000-0002-4911-9462; Karjalainen, J; Uebe, S; https://orcid.org/orcid:0000-0002-4819-7637; Melles, RB; https://orcid.org/orcid:0000-0003-1027-4083; Nair, KS; https://orcid.org/orcid:0000-0001-5309-9727; Luben, R; https://orcid.org/orcid:0000-0002-5088-6343; Simcoe, M; https://orcid.org/orcid:0000-0003-2432-0810; Amersinghe, N; Cree, AJ; https://orcid.org/orcid:0000-0002-1987-8900; Hohn, R; https://orcid.org/orcid:0000-0003-2870-1469; Poplawski, A; Chen, LJ; Rong, S; https://orcid.org/orcid:0000-0001-8352-6363; Aung, T; https://orcid.org/orcid:0000-0002-7916-0589; Vithana, EN; https://orcid.org/orcid:0000-0002-8898-0095; Allingham, RR; Brilliant, M; https://orcid.org/orcid:0000-0002-2753-0699; Budenz, DL; https://orcid.org/orcid:0000-0002-8965-4267; Fingert, JH; https://orcid.org/orcid:0000-0002-0377-0479; Gaasterland, D; Gaasterland, T; Haines, JL; https://orcid.org/orcid:0000-0002-4351-4728; Hauser, M; https://orcid.org/orcid:0000-0003-2667-5420; Lee, RK; Lichter, PR; https://orcid.org/orcid:0000-0001-8394-4813; Liu, Y; https://orcid.org/orcid:0000-0003-2870-4504; Moroi, S; https://orcid.org/orcid:0000-0002-0418-0657; Myers, J; https://orcid.org/orcid:0000-0002-8251-6750; Pericak-Vance, M; https://orcid.org/orcid:0000-0001-7283-8804; Realini, A; Rhee, D; Richards, JE; https://orcid.org/orcid:0000-0003-4808-5931; Ritch, R; https://orcid.org/orcid:0000-0002-9368-7547; Schuman, JS; https://orcid.org/orcid:0000-0002-8885-3766; Scott, WK; https://orcid.org/orcid:0000-0001-9336-6404; Singh, K; Sit, AJ; https://orcid.org/orcid:0000-0002-3904-2625; Vollrath, D; Weinreb, RN; https://orcid.org/orcid:0000-0001-9553-3202; Wollstein, G; https://orcid.org/orcid:0000-0001-7036-2726; Zack, DJ; https://orcid.org/orcid:0000-0002-7966-1973; Sharma, S; https://orcid.org/orcid:0000-0002-0828-025X; Martin, S; Zhou, T; https://orcid.org/orcid:0000-0001-6495-8865; Souzeau, E; https://orcid.org/orcid:0000-0002-2015-6577; Landers, J; https://orcid.org/orcid:0000-0001-8084-5043; Fitzgerald, JT; Mills, RA; https://orcid.org/orcid:0000-0002-7386-2571; Craig, J; https://orcid.org/orcid:0000-0001-9955-9696; Burdon, K; https://orcid.org/orcid:0000-0001-8217-1249; Graham, SL; https://orcid.org/orcid:0000-0001-7519-969X; Casson, RJ; https://orcid.org/orcid:0000-0003-2822-4076; Goldberg, I; https://orcid.org/orcid:0000-0001-7180-6202; White, AJ; https://orcid.org/orcid:0000-0001-6931-5797; Healey, PR; https://orcid.org/orcid:0009-0004-8341-0263; Mackey, DA; https://orcid.org/orcid:0000-0001-7914-4709; Shiono, M; Misumi, K; Kaieda, R; Harada, H; Minami, S; Emi, M; Emoto, N; https://orcid.org/orcid:0000-0003-2026-4057; Daida, H; https://orcid.org/orcid:0000-0002-3867-0961; Miyauchi, K; https://orcid.org/orcid:0000-0001-9553-466X; Murakami, A; https://orcid.org/orcid:0000-0002-0022-2514; Asai, S; https://orcid.org/orcid:0000-0002-7094-4942; Moriyama, M; https://orcid.org/orcid:0000-0002-4617-508X; Takahashi, Y; https://orcid.org/orcid:0000-0003-2543-7543; Fujioka, T; Obara, W; https://orcid.org/orcid:0000-0003-2720-9640; Mori, S; Ito, H; https://orcid.org/orcid:0000-0002-0164-6108; Nagayama, S; https://orcid.org/orcid:0000-0001-9632-914X; Miki, Y; https://orcid.org/orcid:0000-0003-0114-392X; Masumoto, A; Yamada, A; https://orcid.org/orcid:0000-0003-3157-9070
Publisher Information: Nature Research
Publication Year: 2025
Collection: Oxford University Research Archive (ORA)
Description: 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
Document Type: article in journal/newspaper
Language: English
DOI: 10.1038/s41467-020-20851-4
Availability: https://doi.org/10.1038/s41467-020-20851-4; https://ora.ox.ac.uk/objects/uuid:7505dc61-4fd5-4e0f-be5f-04bff137ab86
Rights: info:eu-repo/semantics/openAccess ; CC Attribution (CC BY)
Accession Number: edsbas.6A373ABF
Database: BASE