The University of Southampton
University of Southampton Institutional Repository

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
1-14
Fan, Qiao
7be06794-1c9b-4d6d-b588-0a7baf329428
Pozarickij, Alfred
6633d242-3c13-44af-9c7b-f4666c5c08cb
Tan, Nicholas Y.Q.
afa4afdc-a15c-4f8c-9e91-68735896e73c
Guo, Xiaobo
90baa94f-49a7-43b0-9c1c-37cf6de6f66b
Verhoeven, Virginie J.M.
e1d3f142-4966-4d70-a190-d3454969b807
Vitart, Veronique
1794d62f-7c77-4d28-968f-08226c9db492
Guggenheim, Jeremy A.
215f4513-dd43-4fba-ad93-8b3cdcfab084
Miyake, Masahiro
56697f91-4e60-4bb2-b7c0-700db15bee00
Tideman, J. Willem L.
e427194f-93ba-4f3a-882c-5e3e633a8de0
Khawaja, Anthony P.
ac15cbf1-b21c-4760-80d9-d8ff7ce51e03
Zhang, Liang
216ccbc3-5449-42f1-83af-4303376c07b4
MacGregor, Stuart
81f77fca-a39f-4df5-a60c-c49ab188955d
Höhn, René
1d00b51a-f4ae-46ed-b7bd-a42d97a3955e
Chen, Peng
82c61c46-d33e-45f1-a349-6e62fa51ba7a
Biino, Ginevra
096d1b91-d3d3-49fa-950e-d79592e78bf4
Wedenoja, Juho
3b8e8eb7-2796-44dc-917b-32d155b0d73d
Saffari, Seyed Ehsan
ebff919a-33b1-487a-b829-f38578f2c148
Tedja, Milly S.
0b295e9e-a354-48e1-8d9f-982141299a50
Xie, Jing
d1486705-a5e8-4490-affb-ef4c5d0109fc
Lanca, Carla
41281897-1a0e-4efe-a19a-4a99fc84dfc2
Wang, Ya Xing
8563cc17-118a-4b1b-bbcd-f40176b3698e
Sahebjada, Srujana
ccc2df10-cc67-4766-ae2b-6807a2692afd
Mazur, Johanna
f3e098de-895e-480b-896c-a5460a5068a7
Mirshahi, Alireza
cce05e97-2645-48a8-a773-fd22aea9a41e
Martin, Nicholas G.
c541a23d-0d62-4963-8355-b06ccc947c3f
Yazar, Seyhan
d8e2faf2-954e-4700-8d65-6fea377cf252
Pennell, Craig E.
4edfcf23-0f2c-4b30-bdff-af57116d673c
Yap, Maurice
02c18488-f901-4af9-b8cc-46a3e00b7fb9
Haarman, Annechien E.G.
cfca17d9-7bae-4121-9d52-4bfd96caf333
Enthoven, Clair A.
0c2b2f26-0773-4ee8-8b5b-18df30446b0d
Polling, Jan Roelof
22c84568-1336-4ee4-96ab-2217da01c1e9
Bailey-Wilson, Joan E.
d0cbd495-a84c-4558-a248-e440b13a8517
Veluchamy, Amutha Barathi
b47ab61a-0cda-4b67-83db-8ad9eeb49679
Burdon, Kathryn P.
9bfe89da-62b2-42e2-b34d-7223df070278
Campbell, Harry
3c9b9dc5-2c41-4259-b7a9-465ffc1d0c0d
Chen, Li Jia
2bdb1122-9bc3-4d16-b7dd-d455bcfb4632
Chew, Emily Y.
576b6aef-071c-4f72-be97-ad83467f258a
Craig, Jamie E.
795b9c1d-b781-4a27-90ce-cd0ddaa70a9a
Cumberland, Phillippa M.
e84f09c3-c08c-41b6-9dbc-b366b2120472
Evans, David M.
8621858a-0356-427f-95b6-1a87f5bb2c55
Li, Qing
ca8c2036-8537-4391-a030-66e48d1180e6
Wilson, James F.
2d9db9fe-0368-479c-b28e-8913cc9056f7
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Morgan, James E.
b6ca32d9-658d-4959-8356-381264d54093
Self, Jay
0f6efc58-ae24-4667-b8d6-6fafa849e389
Foster, Paul J.
d58cb374-4307-4319-8e9f-f0ac6092e347
Cheng, Ching Yu
6564b507-eecb-4c54-a63f-d7c652f7b427
et al.
Consortium for Refractive Error and Myopia (CREAM)
UK Biobank Eye and Vision Consortium
Fan, Qiao
7be06794-1c9b-4d6d-b588-0a7baf329428
Pozarickij, Alfred
6633d242-3c13-44af-9c7b-f4666c5c08cb
Tan, Nicholas Y.Q.
afa4afdc-a15c-4f8c-9e91-68735896e73c
Guo, Xiaobo
90baa94f-49a7-43b0-9c1c-37cf6de6f66b
Verhoeven, Virginie J.M.
e1d3f142-4966-4d70-a190-d3454969b807
Vitart, Veronique
1794d62f-7c77-4d28-968f-08226c9db492
Guggenheim, Jeremy A.
215f4513-dd43-4fba-ad93-8b3cdcfab084
Miyake, Masahiro
56697f91-4e60-4bb2-b7c0-700db15bee00
Tideman, J. Willem L.
e427194f-93ba-4f3a-882c-5e3e633a8de0
Khawaja, Anthony P.
ac15cbf1-b21c-4760-80d9-d8ff7ce51e03
Zhang, Liang
216ccbc3-5449-42f1-83af-4303376c07b4
MacGregor, Stuart
81f77fca-a39f-4df5-a60c-c49ab188955d
Höhn, René
1d00b51a-f4ae-46ed-b7bd-a42d97a3955e
Chen, Peng
82c61c46-d33e-45f1-a349-6e62fa51ba7a
Biino, Ginevra
096d1b91-d3d3-49fa-950e-d79592e78bf4
Wedenoja, Juho
3b8e8eb7-2796-44dc-917b-32d155b0d73d
Saffari, Seyed Ehsan
ebff919a-33b1-487a-b829-f38578f2c148
Tedja, Milly S.
0b295e9e-a354-48e1-8d9f-982141299a50
Xie, Jing
d1486705-a5e8-4490-affb-ef4c5d0109fc
Lanca, Carla
41281897-1a0e-4efe-a19a-4a99fc84dfc2
Wang, Ya Xing
8563cc17-118a-4b1b-bbcd-f40176b3698e
Sahebjada, Srujana
ccc2df10-cc67-4766-ae2b-6807a2692afd
Mazur, Johanna
f3e098de-895e-480b-896c-a5460a5068a7
Mirshahi, Alireza
cce05e97-2645-48a8-a773-fd22aea9a41e
Martin, Nicholas G.
c541a23d-0d62-4963-8355-b06ccc947c3f
Yazar, Seyhan
d8e2faf2-954e-4700-8d65-6fea377cf252
Pennell, Craig E.
4edfcf23-0f2c-4b30-bdff-af57116d673c
Yap, Maurice
02c18488-f901-4af9-b8cc-46a3e00b7fb9
Haarman, Annechien E.G.
cfca17d9-7bae-4121-9d52-4bfd96caf333
Enthoven, Clair A.
0c2b2f26-0773-4ee8-8b5b-18df30446b0d
Polling, Jan Roelof
22c84568-1336-4ee4-96ab-2217da01c1e9
Bailey-Wilson, Joan E.
d0cbd495-a84c-4558-a248-e440b13a8517
Veluchamy, Amutha Barathi
b47ab61a-0cda-4b67-83db-8ad9eeb49679
Burdon, Kathryn P.
9bfe89da-62b2-42e2-b34d-7223df070278
Campbell, Harry
3c9b9dc5-2c41-4259-b7a9-465ffc1d0c0d
Chen, Li Jia
2bdb1122-9bc3-4d16-b7dd-d455bcfb4632
Chew, Emily Y.
576b6aef-071c-4f72-be97-ad83467f258a
Craig, Jamie E.
795b9c1d-b781-4a27-90ce-cd0ddaa70a9a
Cumberland, Phillippa M.
e84f09c3-c08c-41b6-9dbc-b366b2120472
Evans, David M.
8621858a-0356-427f-95b6-1a87f5bb2c55
Li, Qing
ca8c2036-8537-4391-a030-66e48d1180e6
Wilson, James F.
2d9db9fe-0368-479c-b28e-8913cc9056f7
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Morgan, James E.
b6ca32d9-658d-4959-8356-381264d54093
Self, Jay
0f6efc58-ae24-4667-b8d6-6fafa849e389
Foster, Paul J.
d58cb374-4307-4319-8e9f-f0ac6092e347
Cheng, Ching Yu
6564b507-eecb-4c54-a63f-d7c652f7b427

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), 1-14, [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.

Text
s42003-020-0802-y - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)

More information

Accepted/In Press date: 24 January 2020
e-pub ahead of print date: 19 March 2020
Published date: 20 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

Catalogue record

Date deposited: 13 Jul 2020 16:31
Last modified: 30 Jun 2022 01:40

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×