Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium, UK Biobank Eye and Vision Consortium

Research output: Contribution to journalArticle

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Original languageEnglish
Article number435
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Genome-Wide Association Study
Optic Disk
optics
Optics
nerve tissue
glaucoma
Genes
loci
Genome
Genetic Loci
genome
Intraocular Pressure
Haplotypes
genetic correlation
Meta-Analysis
haplotypes
genome-wide association study
Primary Open Angle Glaucoma

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International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium, & UK Biobank Eye and Vision Consortium (2019). Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Communications Biology, 2(1), [435]. https://doi.org/10.1038/s42003-019-0634-9
International Glaucoma Genetics Consortium ; NEIGHBORHOOD Consortium ; UK Biobank Eye and Vision Consortium. / Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. In: Communications Biology. 2019 ; Vol. 2, No. 1.
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author = "{International Glaucoma Genetics Consortium} and {NEIGHBORHOOD Consortium} and {UK Biobank Eye and Vision Consortium} and Bonnemaijer, {Pieter W.M.} and Leeuwen, {Elisabeth M.van} and Iglesias, {Adriana I.} and Puya Gharahkhani and Veronique Vitart and Khawaja, {Anthony P.} and Mark Simcoe and Ren{\'e} H{\"o}hn and Cree, {Angela J.} and Igo, {Rob P.} and Burdon, {Kathryn P.} and Craig, {Jamie E.} and Hewitt, {Alex W.} and Jost Jonas and Khor, {Chiea Cheun} and Francesca Pasutto and Mackey, {David A.} and Paul Mitchell and Aniket Mishra and Calvin Pang and Pasquale, {Louis R.} and Henriette Springelkamp and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Viswanathan, {Ananth C.} and Robert Wojciechowski and Tien Wong and Young, {Terrri L.} and Tanja Zeller and Rand Allingham and Don Budenz and Bailey, {Jessica Cooke} and John Fingert and Douglas Gaasterland and Teresa Gaasterland and Haines, {Jonathan L.} and Lisa Hark and Michael Hauser and Kang, {Jae Hee} and Peter Kraft and Richard Lee and Paul Lichter and Yutao Liu and Syoko Moroi and Pasquale, {Louis R.} and Margaret Pericak and Anthony Realini and Doug Rhee and Richards, {Julia R.} and Robert Ritch and Scott, {William K.} and Kuldev Singh and Arthur Sit and Douglas Vollrath and Robert Weinreb and Gadi Wollstein and Wilmer, {Don Zack} and Denize Atan and Tariq Aslam and Barman, {Sarah A.} and Barrett, {Jenny H.} and Paul Bishop and Peter Blows and Catey Bunce and Carare, {Roxana O.} and Usha Chakravarthy and Michelle Chan and Chua, {Sharon Y.L.} and Crabb, {David P.} and Cumberland, {Philippa M.} and Alexander Day and Parul Desai and Bal Dhillon and Dick, {Andrew D.} and Cathy Egan and Sarah Ennis and Paul Foster and Marcus Fruttiger and Gallacher, {John E.J.} and Garway, {David F.} and Jane Gibson and {Dan Gore}, Gore and Guggenheim, {Jeremy A.} and Alison Hardcastle and Harding, {Simon P.} and Hogg, {Ruth E.} and Keane, {Pearse A.} and Khaw, {Peng T.} and Gerassimos Lascaratos and Tom Macgillivray and Sarah Mackie and Keith Martin and Michelle McGaughey and Bernadette McGuinness and McKay, {Gareth J.} and Martin McKibbin and Danny Mitry and Tony Moore and Morgan, {James E.} and Muthy, {Zaynah A.} and Eoin O’Sullivan and Owen, {Chris G.} and Praveen Patel and Euan Paterson and Tunde Peto and Axel Petzold and Rahi, {Jugnoo S.} and Rudnikca, {Alicja R.} and Jay Self and Sobha Sivaprasad and David Steel and Irene Stratton and Nicholas Strouthidis and Cathie Sudlow and Dhanes Thomas and Emanuele Trucco and Adnan Tufail and Vernon, {Stephen A.} and Viswanathan, {Ananth C.} and Cathy Williams and Katie Williams and Woodside, {Jayne V.} and Yates, {Max M.} and Jennifer Yip and Yalin Zheng and Aslihan Gerhold-Ay and Stefan Nickels and Wilson, {James F.} and Caroline Hayward and Boutin, {Thibaud S.} and Ozren Polašek and Tin Aung and Khor, {Chiea Chuen} and Najaf Amin and Lotery, {Andrew J.} and Wiggs, {Janey L.} and Cheng, {Ching Yu} and Hysi, {Pirro G.} and Hammond, {Christopher J.} and Thiadens, {Alberta A.H.J.} and Stuart MacGregor and Klaver, {Caroline C.W.} and Duijn, {Cornelia M.van}",
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International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium & UK Biobank Eye and Vision Consortium 2019, 'Multi-trait genome-wide association study identifies new loci associated with optic disc parameters' Communications Biology, vol. 2, no. 1, 435. https://doi.org/10.1038/s42003-019-0634-9

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. / International Glaucoma Genetics Consortium; NEIGHBORHOOD Consortium; UK Biobank Eye and Vision Consortium.

In: Communications Biology, Vol. 2, No. 1, 435, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

AU - International Glaucoma Genetics Consortium

AU - NEIGHBORHOOD Consortium

AU - UK Biobank Eye and Vision Consortium

AU - Bonnemaijer, Pieter W.M.

AU - Leeuwen, Elisabeth M.van

AU - Iglesias, Adriana I.

AU - Gharahkhani, Puya

AU - Vitart, Veronique

AU - Khawaja, Anthony P.

AU - Simcoe, Mark

AU - Höhn, René

AU - Cree, Angela J.

AU - Igo, Rob P.

AU - Burdon, Kathryn P.

AU - Craig, Jamie E.

AU - Hewitt, Alex W.

AU - Jonas, Jost

AU - Khor, Chiea Cheun

AU - Pasutto, Francesca

AU - Mackey, David A.

AU - Mitchell, Paul

AU - Mishra, Aniket

AU - Pang, Calvin

AU - Pasquale, Louis R.

AU - Springelkamp, Henriette

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Viswanathan, Ananth C.

AU - Wojciechowski, Robert

AU - Wong, Tien

AU - Young, Terrri L.

AU - Zeller, Tanja

AU - Allingham, Rand

AU - Budenz, Don

AU - Bailey, Jessica Cooke

AU - Fingert, John

AU - Gaasterland, Douglas

AU - Gaasterland, Teresa

AU - Haines, Jonathan L.

AU - Hark, Lisa

AU - Hauser, Michael

AU - Kang, Jae Hee

AU - Kraft, Peter

AU - Lee, Richard

AU - Lichter, Paul

AU - Liu, Yutao

AU - Moroi, Syoko

AU - Pasquale, Louis R.

AU - Pericak, Margaret

AU - Realini, Anthony

AU - Rhee, Doug

AU - Richards, Julia R.

AU - Ritch, Robert

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur

AU - Vollrath, Douglas

AU - Weinreb, Robert

AU - Wollstein, Gadi

AU - Wilmer, Don Zack

AU - Atan, Denize

AU - Aslam, Tariq

AU - Barman, Sarah A.

AU - Barrett, Jenny H.

AU - Bishop, Paul

AU - Blows, Peter

AU - Bunce, Catey

AU - Carare, Roxana O.

AU - Chakravarthy, Usha

AU - Chan, Michelle

AU - Chua, Sharon Y.L.

AU - Crabb, David P.

AU - Cumberland, Philippa M.

AU - Day, Alexander

AU - Desai, Parul

AU - Dhillon, Bal

AU - Dick, Andrew D.

AU - Egan, Cathy

AU - Ennis, Sarah

AU - Foster, Paul

AU - Fruttiger, Marcus

AU - Gallacher, John E.J.

AU - Garway, David F.

AU - Gibson, Jane

AU - Dan Gore, Gore

AU - Guggenheim, Jeremy A.

AU - Hardcastle, Alison

AU - Harding, Simon P.

AU - Hogg, Ruth E.

AU - Keane, Pearse A.

AU - Khaw, Peng T.

AU - Lascaratos, Gerassimos

AU - Macgillivray, Tom

AU - Mackie, Sarah

AU - Martin, Keith

AU - McGaughey, Michelle

AU - McGuinness, Bernadette

AU - McKay, Gareth J.

AU - McKibbin, Martin

AU - Mitry, Danny

AU - Moore, Tony

AU - Morgan, James E.

AU - Muthy, Zaynah A.

AU - O’Sullivan, Eoin

AU - Owen, Chris G.

AU - Patel, Praveen

AU - Paterson, Euan

AU - Peto, Tunde

AU - Petzold, Axel

AU - Rahi, Jugnoo S.

AU - Rudnikca, Alicja R.

AU - Self, Jay

AU - Sivaprasad, Sobha

AU - Steel, David

AU - Stratton, Irene

AU - Strouthidis, Nicholas

AU - Sudlow, Cathie

AU - Thomas, Dhanes

AU - Trucco, Emanuele

AU - Tufail, Adnan

AU - Vernon, Stephen A.

AU - Viswanathan, Ananth C.

AU - Williams, Cathy

AU - Williams, Katie

AU - Woodside, Jayne V.

AU - Yates, Max M.

AU - Yip, Jennifer

AU - Zheng, Yalin

AU - Gerhold-Ay, Aslihan

AU - Nickels, Stefan

AU - Wilson, James F.

AU - Hayward, Caroline

AU - Boutin, Thibaud S.

AU - Polašek, Ozren

AU - Aung, Tin

AU - Khor, Chiea Chuen

AU - Amin, Najaf

AU - Lotery, Andrew J.

AU - Wiggs, Janey L.

AU - Cheng, Ching Yu

AU - Hysi, Pirro G.

AU - Hammond, Christopher J.

AU - Thiadens, Alberta A.H.J.

AU - MacGregor, Stuart

AU - Klaver, Caroline C.W.

AU - Duijn, Cornelia M.van

PY - 2019/12/1

Y1 - 2019/12/1

N2 - A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

AB - A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

UR - http://www.scopus.com/inward/record.url?scp=85075712104&partnerID=8YFLogxK

U2 - 10.1038/s42003-019-0634-9

DO - 10.1038/s42003-019-0634-9

M3 - Article

VL - 2

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 435

ER -

International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium, UK Biobank Eye and Vision Consortium. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Communications Biology. 2019 Dec 1;2(1). 435. https://doi.org/10.1038/s42003-019-0634-9