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Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

2399-3642
Fan, Qiao
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Pozarickij, Alfred
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Tan, Nicholas Y.Q.
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Verhoeven, Virginie J.M.
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Khawaja, Anthony P.
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MacGregor, Stuart
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Höhn, René
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Chen, Peng
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Martin, Nicholas G.
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Yazar, Seyhan
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Bailey-Wilson, Joan E.
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Veluchamy, Amutha Barathi
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Burdon, Kathryn P.
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Campbell, Harry
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Chen, Li Jia
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Chew, Emily Y.
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Craig, Jamie E.
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Cumberland, Phillippa M.
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Evans, David M.
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Li, Qing
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Wilson, James F.
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Carare, Roxana O.
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Ennis, Sarah
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Gibson, Jane
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Lotery, Andrew J.
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Foster, Paul J.
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Cheng, Ching Yu
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et al.
Consortium for Refractive Error and Myopia (CREAM)
UK Biobank Eye and Vision Consortium
Fan, Qiao
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Pozarickij, Alfred
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Tan, Nicholas Y.Q.
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Guo, Xiaobo
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Verhoeven, Virginie J.M.
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Vitart, Veronique
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Guggenheim, Jeremy A.
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Miyake, Masahiro
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Tideman, J. Willem L.
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Khawaja, Anthony P.
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Zhang, Liang
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MacGregor, Stuart
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Höhn, René
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Chen, Peng
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Biino, Ginevra
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Wedenoja, Juho
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Lanca, Carla
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Wang, Ya Xing
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Sahebjada, Srujana
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Mazur, Johanna
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Mirshahi, Alireza
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Martin, Nicholas G.
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Yazar, Seyhan
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Yap, Maurice
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Haarman, Annechien E.G.
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Enthoven, Clair A.
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Polling, Jan Roelof
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Bailey-Wilson, Joan E.
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Veluchamy, Amutha Barathi
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Burdon, Kathryn P.
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Campbell, Harry
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Chen, Li Jia
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Chew, Emily Y.
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Craig, Jamie E.
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Cumberland, Phillippa M.
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Evans, David M.
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Li, Qing
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Wilson, James F.
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Carare, Roxana O.
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Ennis, Sarah
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Gibson, Jane
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Lotery, Andrew J.
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Morgan, James E.
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Self, Jay
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Foster, Paul J.
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Cheng, Ching Yu
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Fan, Qiao, Pozarickij, Alfred and Tan, Nicholas Y.Q. , et al., Consortium for Refractive Error and Myopia (CREAM) and UK Biobank Eye and Vision Consortium (2020) Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error. Communications Biology, 3 (1), [133]. (doi:10.1038/s42003-020-0802-y).

Record type: Article

Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

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s42003-020-0802-y - Version of Record
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Accepted/In Press date: 24 January 2020
e-pub ahead of print date: 19 March 2020
Published date: 19 March 2020

Identifiers

Local EPrints ID: 442321
URI: http://eprints.soton.ac.uk/id/eprint/442321
ISSN: 2399-3642
PURE UUID: 40d23222-72b9-435a-8408-1d4d3a41bc79
ORCID for Roxana O. Carare: ORCID iD orcid.org/0000-0001-6458-3776
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jay Self: ORCID iD orcid.org/0000-0002-1030-9963

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Date deposited: 13 Jul 2020 16:31
Last modified: 17 Mar 2024 03:04

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Contributors

Author: Qiao Fan
Author: Alfred Pozarickij
Author: Nicholas Y.Q. Tan
Author: Xiaobo Guo
Author: Virginie J.M. Verhoeven
Author: Veronique Vitart
Author: Jeremy A. Guggenheim
Author: Masahiro Miyake
Author: J. Willem L. Tideman
Author: Anthony P. Khawaja
Author: Liang Zhang
Author: Stuart MacGregor
Author: René Höhn
Author: Peng Chen
Author: Ginevra Biino
Author: Juho Wedenoja
Author: Seyed Ehsan Saffari
Author: Milly S. Tedja
Author: Jing Xie
Author: Carla Lanca
Author: Ya Xing Wang
Author: Srujana Sahebjada
Author: Johanna Mazur
Author: Alireza Mirshahi
Author: Nicholas G. Martin
Author: Seyhan Yazar
Author: Craig E. Pennell
Author: Maurice Yap
Author: Annechien E.G. Haarman
Author: Clair A. Enthoven
Author: Jan Roelof Polling
Author: Joan E. Bailey-Wilson
Author: Amutha Barathi Veluchamy
Author: Kathryn P. Burdon
Author: Harry Campbell
Author: Li Jia Chen
Author: Emily Y. Chew
Author: Jamie E. Craig
Author: Phillippa M. Cumberland
Author: David M. Evans
Author: Qing Li
Author: James F. Wilson
Author: Sarah Ennis ORCID iD
Author: Jane Gibson ORCID iD
Author: James E. Morgan
Author: Jay Self ORCID iD
Author: Paul J. Foster
Author: Ching Yu Cheng
Corporate Author: et al.
Corporate Author: Consortium for Refractive Error and Myopia (CREAM)
Corporate Author: UK Biobank Eye and Vision Consortium

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