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

NEIGHBORHOOD Consortium; ANZRAG Consortium; Biobank Japan project; FinnGen study; UK Biobank Eye and Vision Consortium; GIGA study group; 23 and Me Research Team; Ayub Qassim; Owen M. Siggs; Shiwani Sharma; Sarah Martin; Tiger Zhou; Emmanuelle Souzeau; John Landers; Jude T. Fitzgerald; Richard A. Mills; Jamie E. Craig; Kathryn Burdon

doi:10.1038/s41467-020-20851-4

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

NEIGHBORHOOD Consortium, ANZRAG Consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Ayub Qassim, Owen M. Siggs, Shiwani Sharma, Sarah Martin, Tiger Zhou, Emmanuelle Souzeau, John Landers, Jude T. Fitzgerald, Richard A. Mills, Jamie E. Craig, Kathryn Burdon

College of Medicine and Public Health

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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
Article number	1258
Number of pages	16
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20851-4
Publication status	Published - 24 Feb 2021

Keywords

Primary open-angle glaucoma (POAG)
blindness

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10.1038/s41467-020-20851-4Licence: CC BY

Final published versionFinal published version, 2.52 MBLicence: CC BY

Cite this

NEIGHBORHOOD Consortium, ANZRAG Consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Qassim, A., Siggs, O. M., Sharma, S., Martin, S., Zhou, T., Souzeau, E., Landers, J., Fitzgerald, J. T., Mills, R. A., Craig, J. E., & Burdon, K. (2021). Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nature Communications, 12(1), Article 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.",

keywords = "Primary open-angle glaucoma (POAG), blindness",

author = "{NEIGHBORHOOD Consortium} and {ANZRAG Consortium} and {Biobank Japan project} and {FinnGen study} and {UK Biobank Eye and Vision Consortium} and {GIGA study group} and {23 and Me Research Team} and 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 Rong, {Shi Song} and Tin Aung and Vithana, {Eranga Nishanthie} and Allingham, {R. Rand} and Murray Brilliant and Budenz, {Donald L.} and Bailey, {Jessica N.Cooke} and Fingert, {John H.} and Douglas Gaasterland and Teresa Gaasterland and Haines, {Jonathan L.} and Michael Hauser and Lee, {Richard K.} and Lichter, {Paul R.} and Yutao Liu and Syoko Moroi and Jonathan Myers and Margaret Pericak-Vance and Anthony Realini and Doug Rhee and Richards, {Julia E.} and Robert Ritch and Schuman, {Joel S.} and Scott, {William K.} and Kuldev Singh and Sit, {Arthur J.} and Douglas Vollrath and Weinreb, {Robert N.} and Gadi Wollstein and Zack, {Donald J.} and Shiwani Sharma and Sarah Martin and Tiger Zhou and Emmanuelle Souzeau and John Landers and Fitzgerald, {Jude T.} and Mills, {Richard A.} and Craig, {Jamie E.} and Kathryn Burdon and Graham, {Stuart L.} and Casson, {Robert J.} and Ivan Goldberg and White, {Andrew J.} and Healey, {Paul R.} and Mackey, {David A.} and Hewitt, {Alex W.} and Masaki Shiono and Kazuo Misumi and Reiji Kaieda and Hiromasa Harada and Shiro Minami and Mitsuru Emi and Naoya Emoto and Hiroyuki Daida and Katsumi Miyauchi and Akira Murakami and Satoshi Asai and Mitsuhiko Moriyama and Yasuo Takahashi and Tomoaki Fujioka and Wataru Obara and Seijiro Mori and Hideki Ito and Satoshi Nagayama and Yoshio Miki and Akihide Masumoto and Akira Yamada and Yasuko Nishizawa and Ken Kodama and Hiromu Kutsumi and Yoshihisa Sugimoto and Yukihiro Koretsune and Hideo Kusuoka and Hideki Yanaiag and Akiko Nagai and Makoto Hirata and Yoichiro Kamatani and Kaori Muto and Koichi Matsuda and Yutaka Kiyohara and Toshiharu Ninomiya and Akiko Tamakoshi and Zentaro Yamagata and Taisei Mushiroda and Yoshinori Murakami and Koichiro Yuji and Yoichi Furukawa and Hitoshi Zembutsu and Toshihiro Tanaka and Yozo Ohnishi and Yusuke Nakamura and Anu Jalanko and Jaakko Kaprio and Kati Donner and Mari Kaunisto and Nina Mars and Alexander Dada and Anastasia Shcherban and Andrea Ganna and Arto Lehisto and Elina Kilpel{\"a}inen and Georg Brein and Ghazal Awaisa and Jarmo Harju and Kalle P{\"a}rn and {Della Briotta Parolo}, Pietro and Risto Kajanne and Susanna Lemmel{\"a} and Sipil{\"a}, {Timo P.} and Tuomas Sipil{\"a} and Ulrike Lyhs and Vincent Llorens and Teemu Niiranen and Kati Kristiansson and Lotta M{\"a}nnikk{\"o} and Jim{\'e}nez, {Manuel Gonz{\'a}lez} and Markus Perola and Regis Wong and Terhi Kilpi and Tero Hiekkalinna and Elina J{\"a}rvensivu and Essi Kaiharju and Hannele Mattsson and Markku Laukkanen and P{\"a}ivi Laiho and Sini L{\"a}hteenm{\"a}ki and Tuuli Sistonen and Sirpa Soini and Adam Ziemann and Anne Lehtonen and Apinya Lertratanakul and Bob Georgantas and Bridget Riley-Gillis and Danjuma Quarless and Fedik Rahimov and Graham Heap and Howard Jacob and Jeffrey Waring and Davis, {Justin Wade} and Nizar Smaoui and Relja Popovic and Sahar Esmaeeli and Jeff Waring and Athena Matakidou and Ben Challis and David Close and Slav{\'e} Petrovski and Antti Karlsson and Johanna Schleutker and Kari Pulkki and Petri Virolainen and Lila Kallio and Arto Mannermaa and Sami Heikkinen and Kosma, {Veli Matti} and Chen, {Chia Yen} and Heiko Runz and Jimmy Liu and Paola Bronson and Sally John and Sanni Lahdenper{\"a} and Susan Eaton and Wei Zhou and Minna Hendolin and Outi Tuovila and Raimo Pakkanen and Joseph Maranville and Keith Usiskin and Marla Hochfeld and Robert Plenge and Robert Yang and Shameek Biswas and Steven Greenberg and Eija Laakkonen and Juha Kononen and Juha Paloneva and Urho Kujala and Teijo Kuopio and Jari Laukkanen and Eeva Kangasniemi and Kimmo Savinainen and Reijo Laaksonen and Mikko Arvas and Jarmo Ritari and Jukka Partanen and Kati Hyv{\"a}rinen and Tiina Wahlfors and Andrew Peterson and Danny Oh and Diana Chang and Edmond Teng and Erich Strauss and Geoff Kerchner and Hao Chen and Hubert Chen and Jennifer Schutzman and John Michon and Julie Hunkapiller and Mark McCarthy and Natalie Bowers and Tim Lu and Tushar Bhangale and David Pulford and Dawn Waterworth and Diptee Kulkarni and Fanli Xu and Jo Betts and Gordillo, {Jorge Esparza} and Joshua Hoffman and Kirsi Auro and Linda McCarthy and Soumitra Ghosh and Meg Ehm and Kimmo Pitk{\"a}nen and Tomi M{\"a}kel{\"a} and Anu Loukola",

year = "2021",

month = feb,

day = "24",

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

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature",

number = "1",

}

NEIGHBORHOOD Consortium, ANZRAG Consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Qassim, A, Siggs, OM, Sharma, S, Martin, S, Zhou, T, Souzeau, E , Landers, J, Fitzgerald, JT, Mills, RA , Craig, JE & Burdon, K 2021, 'Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries', Nature Communications, vol. 12, no. 1, 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 - NEIGHBORHOOD Consortium

AU - ANZRAG Consortium

AU - Biobank Japan project

AU - FinnGen study

AU - UK Biobank Eye and Vision Consortium

AU - GIGA study group

AU - 23 and Me Research Team

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 - Allingham, R. Rand

AU - Brilliant, Murray

AU - Budenz, Donald L.

AU - Bailey, Jessica N.Cooke

AU - Fingert, John H.

AU - Gaasterland, Douglas

AU - Gaasterland, Teresa

AU - Haines, Jonathan L.

AU - Hauser, Michael

AU - Lee, Richard K.

AU - Lichter, Paul R.

AU - Liu, Yutao

AU - Moroi, Syoko

AU - Myers, Jonathan

AU - Pericak-Vance, Margaret

AU - Realini, Anthony

AU - Rhee, Doug

AU - Richards, Julia E.

AU - Ritch, Robert

AU - Schuman, Joel S.

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur J.

AU - Vollrath, Douglas

AU - Weinreb, Robert N.

AU - Wollstein, Gadi

AU - Zack, Donald J.

AU - Sharma, Shiwani

AU - Martin, Sarah

AU - Zhou, Tiger

AU - Souzeau, Emmanuelle

AU - Landers, John

AU - Fitzgerald, Jude T.

AU - Mills, Richard A.

AU - Craig, Jamie E.

AU - Burdon, Kathryn

AU - Graham, Stuart L.

AU - Casson, Robert J.

AU - Goldberg, Ivan

AU - White, Andrew J.

AU - Healey, Paul R.

AU - Mackey, David A.

AU - Hewitt, Alex W.

AU - Shiono, Masaki

AU - Misumi, Kazuo

AU - Kaieda, Reiji

AU - Harada, Hiromasa

AU - Minami, Shiro

AU - Emi, Mitsuru

AU - Emoto, Naoya

AU - Daida, Hiroyuki

AU - Miyauchi, Katsumi

AU - Murakami, Akira

AU - Asai, Satoshi

AU - Moriyama, Mitsuhiko

AU - Takahashi, Yasuo

AU - Fujioka, Tomoaki

AU - Obara, Wataru

AU - Mori, Seijiro

AU - Ito, Hideki

AU - Nagayama, Satoshi

AU - Miki, Yoshio

AU - Masumoto, Akihide

AU - Yamada, Akira

AU - Nishizawa, Yasuko

AU - Kodama, Ken

AU - Kutsumi, Hiromu

AU - Sugimoto, Yoshihisa

AU - Koretsune, Yukihiro

AU - Kusuoka, Hideo

AU - Yanaiag, Hideki

AU - Nagai, Akiko

AU - Hirata, Makoto

AU - Kamatani, Yoichiro

AU - Muto, Kaori

AU - Matsuda, Koichi

AU - Kiyohara, Yutaka

AU - Ninomiya, Toshiharu

AU - Tamakoshi, Akiko

AU - Yamagata, Zentaro

AU - Mushiroda, Taisei

AU - Murakami, Yoshinori

AU - Yuji, Koichiro

AU - Furukawa, Yoichi

AU - Zembutsu, Hitoshi

AU - Tanaka, Toshihiro

AU - Ohnishi, Yozo

AU - Nakamura, Yusuke

AU - Jalanko, Anu

AU - Kaprio, Jaakko

AU - Donner, Kati

AU - Kaunisto, Mari

AU - Mars, Nina

AU - Dada, Alexander

AU - Shcherban, Anastasia

AU - Ganna, Andrea

AU - Lehisto, Arto

AU - Kilpeläinen, Elina

AU - Brein, Georg

AU - Awaisa, Ghazal

AU - Harju, Jarmo

AU - Pärn, Kalle

AU - Della Briotta Parolo, Pietro

AU - Kajanne, Risto

AU - Lemmelä, Susanna

AU - Sipilä, Timo P.

AU - Sipilä, Tuomas

AU - Lyhs, Ulrike

AU - Llorens, Vincent

AU - Niiranen, Teemu

AU - Kristiansson, Kati

AU - Männikkö, Lotta

AU - Jiménez, Manuel González

AU - Perola, Markus

AU - Wong, Regis

AU - Kilpi, Terhi

AU - Hiekkalinna, Tero

AU - Järvensivu, Elina

AU - Kaiharju, Essi

AU - Mattsson, Hannele

AU - Laukkanen, Markku

AU - Laiho, Päivi

AU - Lähteenmäki, Sini

AU - Sistonen, Tuuli

AU - Soini, Sirpa

AU - Ziemann, Adam

AU - Lehtonen, Anne

AU - Lertratanakul, Apinya

AU - Georgantas, Bob

AU - Riley-Gillis, Bridget

AU - Quarless, Danjuma

AU - Rahimov, Fedik

AU - Heap, Graham

AU - Jacob, Howard

AU - Waring, Jeffrey

AU - Davis, Justin Wade

AU - Smaoui, Nizar

AU - Popovic, Relja

AU - Esmaeeli, Sahar

AU - Waring, Jeff

AU - Matakidou, Athena

AU - Challis, Ben

AU - Close, David

AU - Petrovski, Slavé

AU - Karlsson, Antti

AU - Schleutker, Johanna

AU - Pulkki, Kari

AU - Virolainen, Petri

AU - Kallio, Lila

AU - Mannermaa, Arto

AU - Heikkinen, Sami

AU - Kosma, Veli Matti

AU - Chen, Chia Yen

AU - Runz, Heiko

AU - Liu, Jimmy

AU - Bronson, Paola

AU - John, Sally

AU - Lahdenperä, Sanni

AU - Eaton, Susan

AU - Zhou, Wei

AU - Hendolin, Minna

AU - Tuovila, Outi

AU - Pakkanen, Raimo

AU - Maranville, Joseph

AU - Usiskin, Keith

AU - Hochfeld, Marla

AU - Plenge, Robert

AU - Yang, Robert

AU - Biswas, Shameek

AU - Greenberg, Steven

AU - Laakkonen, Eija

AU - Kononen, Juha

AU - Paloneva, Juha

AU - Kujala, Urho

AU - Kuopio, Teijo

AU - Laukkanen, Jari

AU - Kangasniemi, Eeva

AU - Savinainen, Kimmo

AU - Laaksonen, Reijo

AU - Arvas, Mikko

AU - Ritari, Jarmo

AU - Partanen, Jukka

AU - Hyvärinen, Kati

AU - Wahlfors, Tiina

AU - Peterson, Andrew

AU - Oh, Danny

AU - Chang, Diana

AU - Teng, Edmond

AU - Strauss, Erich

AU - Kerchner, Geoff

AU - Chen, Hao

AU - Chen, Hubert

AU - Schutzman, Jennifer

AU - Michon, John

AU - Hunkapiller, Julie

AU - McCarthy, Mark

AU - Bowers, Natalie

AU - Lu, Tim

AU - Bhangale, Tushar

AU - Pulford, David

AU - Waterworth, Dawn

AU - Kulkarni, Diptee

AU - Xu, Fanli

AU - Betts, Jo

AU - Gordillo, Jorge Esparza

AU - Hoffman, Joshua

AU - Auro, Kirsi

AU - McCarthy, Linda

AU - Ghosh, Soumitra

AU - Ehm, Meg

AU - Pitkänen, Kimmo

AU - Mäkelä, Tomi

AU - Loukola, Anu

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.

KW - Primary open-angle glaucoma (POAG)

KW - blindness

UR - http://www.scopus.com/inward/record.url?scp=85101839427&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/nhmrc/1107098

UR - http://purl.org/au-research/grants/nhmrc/1116360

UR - http://purl.org/au-research/grants/nhmrc/1116495

UR - http://purl.org/au-research/grants/nhmrc/1023911

UR - http://purl.org/au-research/grants/nhmrc/1173390

U2 - 10.1038/s41467-020-20851-4

DO - 10.1038/s41467-020-20851-4

M3 - Article

C2 - 33627673

AN - SCOPUS:85101839427

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1258

ER -

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

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