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

Puya Gharahkhani; Eric Jorgenson; Pirro Hysi; Anthony P Khawaja; Sarah Pendergrass; Xikun Han; Jue Sheng Ong; Alex W Hewitt; Ayellet V Segrè; John M Rouhana; Andrew R Hamel; Robert P Igo; Helene Choquet; Ayub Qassim; Navya S Josyula; Jessica N Cooke Bailey; Pieter W M Bonnemaijer; Adriana Iglesias; Owen M Siggs; Terri L Young; Veronique Vitart; Alberta A H J Thiadens; Juha Karjalainen; Steffen Uebe; Ronald B Melles; K Saidas Nair; Robert Luben; Mark Simcoe; Nishani Amersinghe; Angela J Cree; Rene Hohn; Alicia Poplawski; Li Jia Chen; Shi-Song Rong; Tin Aung; Eranga Nishanthie Vithana; Gen Tamiya; Yukihiro Shiga; Masayuki Yamamoto; Toru Nakazawa; Hannah Currant; Ewan Birney; Xin Wang; Adam Auton; Michelle K Lupton; Nicholas G Martin; Adeyinka Ashaye; Olusola Olawoye; Susan E Williams; Stephen Akafo

doi:10.1038/s41467-020-20851-4

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

Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W Hewitt, Ayellet V Segrè, John M Rouhana, Andrew R Hamel, Robert P Igo, Helene Choquet, Ayub Qassim, Navya S Josyula, Jessica N Cooke Bailey, Pieter W M Bonnemaijer, Adriana Iglesias, Owen M Siggs, Terri L YoungVeronique Vitart, Alberta A H J Thiadens, Juha Karjalainen, Steffen Uebe, Ronald B Melles, K Saidas Nair, Robert Luben, Mark Simcoe, Nishani Amersinghe, Angela J Cree, Rene Hohn, Alicia Poplawski, Li Jia Chen, Shi-Song Rong, Tin Aung, Eranga Nishanthie Vithana, , Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Michelle K Lupton, Nicholas G Martin, Adeyinka Ashaye, Olusola Olawoye, Susan E Williams, Stephen Akafo

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1258
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20851-4
Publication status	Published - 24 Feb 2021

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Gharahkhani, P., Jorgenson, E., Hysi, P., Khawaja, A. P., Pendergrass, S., Han, X., Ong, J. S., Hewitt, A. W., Segrè, A. V., Rouhana, J. M., Hamel, A. R., Igo, R. P., Choquet, H., Qassim, A., Josyula, N. S., Cooke Bailey, J. N., Bonnemaijer, P. W. M., Iglesias, A., Siggs, O. M., ... Akafo, S. (2021). Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nature Communications, 12(1), 1258. https://doi.org/10.1038/s41467-020-20851-4

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

abstract = "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.",

author = "Puya Gharahkhani and Eric Jorgenson and Pirro Hysi and Khawaja, {Anthony P} and Sarah Pendergrass and Xikun Han and Ong, {Jue Sheng} and Hewitt, {Alex W} and Segr{\`e}, {Ayellet V} and Rouhana, {John M} and Hamel, {Andrew R} and Igo, {Robert P} and Helene Choquet and Ayub Qassim and Josyula, {Navya S} and {Cooke Bailey}, {Jessica N} and Bonnemaijer, {Pieter W M} and Adriana Iglesias and Siggs, {Owen M} and Young, {Terri L} and Veronique Vitart and Thiadens, {Alberta A H J} and Juha Karjalainen and Steffen Uebe and Melles, {Ronald B} and Nair, {K Saidas} and Robert Luben and Mark Simcoe and Nishani Amersinghe and Cree, {Angela J} and Rene Hohn and Alicia Poplawski and Chen, {Li Jia} and Shi-Song Rong and Tin Aung and Vithana, {Eranga Nishanthie} and Gen Tamiya and Yukihiro Shiga and Masayuki Yamamoto and Toru Nakazawa and Hannah Currant and Ewan Birney and Xin Wang and Adam Auton and Lupton, {Michelle K} and Martin, {Nicholas G} and Adeyinka Ashaye and Olusola Olawoye and Williams, {Susan E} and Stephen Akafo",

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doi = "10.1038/s41467-020-20851-4",

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Gharahkhani, P, Jorgenson, E, Hysi, P, Khawaja, AP, Pendergrass, S, Han, X, Ong, JS, Hewitt, AW, Segrè, AV, Rouhana, JM, Hamel, AR, Igo, RP, Choquet, H, Qassim, A, Josyula, NS, Cooke Bailey, JN, Bonnemaijer, PWM, Iglesias, A, Siggs, OM, Young, TL, Vitart, V, Thiadens, AAHJ, Karjalainen, J, Uebe, S, Melles, RB, Nair, KS, Luben, R, Simcoe, M, Amersinghe, N, Cree, AJ, Hohn, R, Poplawski, A, Chen, LJ, Rong, S-S, Aung, T, Vithana, EN, Tamiya, G, Shiga, Y, Yamamoto, M, Nakazawa, T, Currant, H, Birney, E, Wang, X, Auton, A, Lupton, MK, Martin, NG, Ashaye, A, Olawoye, O & Williams, SE & Akafo, S 2021, 'Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries', Nature Communications, vol. 12, no. 1, pp. 1258. https://doi.org/10.1038/s41467-020-20851-4

TY - JOUR

T1 - Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

AU - Gharahkhani, Puya

AU - Jorgenson, Eric

AU - Hysi, Pirro

AU - Khawaja, Anthony P

AU - Pendergrass, Sarah

AU - Han, Xikun

AU - Ong, Jue Sheng

AU - Hewitt, Alex W

AU - Segrè, Ayellet V

AU - Rouhana, John M

AU - Hamel, Andrew R

AU - Igo, Robert P

AU - Choquet, Helene

AU - Qassim, Ayub

AU - Josyula, Navya S

AU - Cooke Bailey, Jessica N

AU - Bonnemaijer, Pieter W M

AU - Iglesias, Adriana

AU - Siggs, Owen M

AU - Young, Terri L

AU - Vitart, Veronique

AU - Thiadens, Alberta A H J

AU - Karjalainen, Juha

AU - Uebe, Steffen

AU - Melles, Ronald B

AU - Nair, K Saidas

AU - Luben, Robert

AU - Simcoe, Mark

AU - Amersinghe, Nishani

AU - Cree, Angela J

AU - Hohn, Rene

AU - Poplawski, Alicia

AU - Chen, Li Jia

AU - Rong, Shi-Song

AU - Aung, Tin

AU - Vithana, Eranga Nishanthie

AU - Tamiya, Gen

AU - Shiga, Yukihiro

AU - Yamamoto, Masayuki

AU - Nakazawa, Toru

AU - Currant, Hannah

AU - Birney, Ewan

AU - Wang, Xin

AU - Auton, Adam

AU - Lupton, Michelle K

AU - Martin, Nicholas G

AU - Ashaye, Adeyinka

AU - Olawoye, Olusola

AU - Williams, Susan E

AU - Akafo, Stephen

PY - 2021/2/24

Y1 - 2021/2/24

N2 - 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.

AB - 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.

UR - https://www.mendeley.com/catalogue/c15280af-1d54-30d4-9b9a-17a78e44be5d/

U2 - 10.1038/s41467-020-20851-4

DO - 10.1038/s41467-020-20851-4

M3 - Article

C2 - 33627673

SN - 2041-1723

VL - 12

SP - 1258

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

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