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

by Cooke Bailey, Jessica N. , Choquet, Helene , Hewitt, Alex W. , Wang, Xin , Pang, Chi Pui , Han, Xikun , Olawoye, Olusola , Melles, Ronald B. , Akiyama, Masato , Pasquale, Louis R. , Morgan, James E. , Chen, Li Jia , Iglesias, Adriana , Kamatani, Yoichiro , Currant, Hannah , Pasutto, Francesca , Mitchell, Paul , Kubo, Michiaki , Segrè, Ayellet V. , Khawaja, Anthony P. , Tamiya, Gen , Rong, Shi-Song , Shiga, Yukihiro , Yamamoto, Masayuki , Cheng, Ching-Yu , Vithana, Eranga Nishanthie , Lupton, Michelle K. , van Duijn, Cornelia , Klaver, Caroline C. W. , Haines, Jonathan L. , Hysi, Pirro , Craig, Jamie E. , Pendergrass, Sarah , Hamel, Andrew R. , Poplawski, Alicia , Kraft, Peter , Thiadens, Alberta A. H. J. , Uebe, Steffen , Ashaye, Adeyinka , Martin, Nicholas G. , Momozawa, Yukihide , Wiggs, Janey L. , Bonnemaijer, Pieter W. M. , Auton, Adam , Akafo, Stephen , Cree, Angela J. , Hohn, Rene , Birney, Ewan , Josyula, Navya S. , Simcoe, Mark , Rouhana, John M. , Vitart, Veronique , Karjalainen, Juha , Gharahkhani, Puya , Amersinghe, Nishani , Mackey, David A. , Nakazawa, Toru , Khor, Chiea Chuen , Ong, Jue Sheng , Hashimoto, Kazuki , Ramsay, Michele , Nair, K. Saidas , Youn

in 45 / 45/43 / 631/208/205/2138 / 692/699/3161/3172 / Asian People / Blindness / Ethnic factors / Gene mapping / Genes / Genetic Loci - genetics / Genetic Predisposition to Disease - genetics / Genome-wide association studies / Genome-Wide Association Study - methods / Genomes / Genotype / Glaucoma / Glaucoma, Open-Angle - genetics / Humanities and Social Sciences / Humans / Loci / Mapping / Meta-analysis / multidisciplinary / Pathogenesis / Polymorphism, Single Nucleotide - genetics / Risk / Science / Science (multidisciplinary) / White People / Yes-associated protein

2021

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

2021

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2021

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Journal Article

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

Cooke Bailey, Jessica N.,

Choquet, Helene,

Hewitt, Alex W.,

Wang, Xin,

Pang, Chi Pui,

Han, Xikun,

Olawoye, Olusola,

Melles, Ronald B.,

Akiyama, Masato,

Pasquale, Louis R.,

Morgan, James E.,

Chen, Li Jia,

Iglesias, Adriana,

Kamatani, Yoichiro,

Currant, Hannah,

Pasutto, Francesca,

Mitchell, Paul,

Kubo, Michiaki,

Segrè, Ayellet V.,

Khawaja, Anthony P.,

Tamiya, Gen,

Rong, Shi-Song,

Shiga, Yukihiro,

Yamamoto, Masayuki,

Cheng, Ching-Yu,

Vithana, Eranga Nishanthie,

Lupton, Michelle K.,

van Duijn, Cornelia,

Klaver, Caroline C. W.,

Haines, Jonathan L.,

Hysi, Pirro,

Craig, Jamie E.,

Pendergrass, Sarah,

Hamel, Andrew R.,

Poplawski, Alicia,

Kraft, Peter,

Thiadens, Alberta A. H. J.,

Uebe, Steffen,

Ashaye, Adeyinka,

Martin, Nicholas G.,

Momozawa, Yukihide,

Wiggs, Janey L.,

Bonnemaijer, Pieter W. M.,

Auton, Adam,

Akafo, Stephen,

Cree, Angela J.,

Hohn, Rene,

Birney, Ewan,

Josyula, Navya S.,

Simcoe, Mark,

Rouhana, John M.,

Vitart, Veronique,

Karjalainen, Juha,

Gharahkhani, Puya,

Amersinghe, Nishani,

Mackey, David A.,

Nakazawa, Toru,

Khor, Chiea Chuen,

Ong, Jue Sheng,

Hashimoto, Kazuki,

Ramsay, Michele,

Nair, K. Saidas,

Youn

2021

Overview

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. Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 45/43