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

Qiao Fan; Alfred Pozarickij; Nicholas Y.Q. Tan; Xiaobo Guo; Virginie J.M. Verhoeven; Veronique Vitart; Jeremy A. Guggenheim; Masahiro Miyake; J. Willem L. Tideman; Anthony P. Khawaja; Liang Zhang; Stuart MacGregor; René Höhn; Peng Chen; Ginevra Biino; Juho Wedenoja; Seyed Ehsan Saffari; Milly S. Tedja; Jing Xie; Carla Lanca; Ya Xing Wang; Srujana Sahebjada; Johanna Mazur; Alireza Mirshahi; Nicholas G. Martin; Seyhan Yazar; Craig E. Pennell; Maurice Yap; Annechien E.G. Haarman; Clair A. Enthoven; Jan Roelof Polling; Joan E. Bailey-Wilson; Amutha Barathi Veluchamy; Kathryn P. Burdon; Harry Campbell; Li Jia Chen; Emily Y. Chew; Jamie E. Craig; Phillippa M. Cumberland; Margaret M. Deangelis; Cécile Delcourt; Xiaohu Ding; David M. Evans; Puya Gharahkhani; Adriana I. Iglesias; Toomas Haller; Xikun Han; Quan Hoang; Robert P. Igo; Shea Ping Yip

doi:10.1038/s42003-020-0802-y

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

Qiao Fan, Alfred Pozarickij, Nicholas Y.Q. Tan, Xiaobo Guo, Virginie J.M. Verhoeven, Veronique Vitart, Jeremy A. Guggenheim, Masahiro Miyake, J. Willem L. Tideman, Anthony P. Khawaja, Liang Zhang, Stuart MacGregor, René Höhn, Peng Chen, Ginevra Biino, Juho Wedenoja, Seyed Ehsan Saffari, Milly S. Tedja, Jing Xie, Carla LancaYa Xing Wang, Srujana Sahebjada, Johanna Mazur, Alireza Mirshahi, Nicholas G. Martin, Seyhan Yazar, Craig E. Pennell, Maurice Yap, Annechien E.G. Haarman, Clair A. Enthoven, Jan Roelof Polling, Joan E. Bailey-Wilson, Amutha Barathi Veluchamy, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Emily Y. Chew, Jamie E. Craig, Phillippa M. Cumberland, Margaret M. Deangelis, Cécile Delcourt, Xiaohu Ding, David M. Evans, Puya Gharahkhani, Adriana I. Iglesias, Toomas Haller, Xikun Han, Quan Hoang, Robert P. Igo, Shea Ping Yip

Research output: Journal article publication › Journal article › Academic research › peer-review

23 Citations (Scopus)

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.

Original language	English
Article number	133
Journal	Communications Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-0802-y
Publication status	Published - 19 Mar 2020

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences
Medicine (miscellaneous)

More information

10.1038/s42003-020-0802-y

http://hdl.handle.net/10397/92797

Cite this

Fan, Q., Pozarickij, A., Tan, N. Y. Q., Guo, X., Verhoeven, V. J. M., Vitart, V., Guggenheim, J. A., Miyake, M., Tideman, J. W. L., Khawaja, A. P., Zhang, L., MacGregor, S., Höhn, R., Chen, P., Biino, G., Wedenoja, J., Saffari, S. E., Tedja, M. S., Xie, J., ... Yip, S. P. (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), Article 133. https://doi.org/10.1038/s42003-020-0802-y

@article{60aa1b492b5c4c94a1b3da7707629148,

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

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.",

author = "Qiao Fan and Alfred Pozarickij and Tan, {Nicholas Y.Q.} and Xiaobo Guo and Verhoeven, {Virginie J.M.} and Veronique Vitart and Guggenheim, {Jeremy A.} and Masahiro Miyake and Tideman, {J. Willem L.} and Khawaja, {Anthony P.} and Liang Zhang and Stuart MacGregor and Ren{\'e} H{\"o}hn and Peng Chen and Ginevra Biino and Juho Wedenoja and Saffari, {Seyed Ehsan} and Tedja, {Milly S.} and Jing Xie and Carla Lanca and Wang, {Ya Xing} and Srujana Sahebjada and Johanna Mazur and Alireza Mirshahi and Martin, {Nicholas G.} and Seyhan Yazar and Pennell, {Craig E.} and Maurice Yap and Haarman, {Annechien E.G.} and Enthoven, {Clair A.} and Polling, {Jan Roelof} and Bailey-Wilson, {Joan E.} and Veluchamy, {Amutha Barathi} and Burdon, {Kathryn P.} and Harry Campbell and Chen, {Li Jia} and Chew, {Emily Y.} and Craig, {Jamie E.} and Cumberland, {Phillippa M.} and Deangelis, {Margaret M.} and C{\'e}cile Delcourt and Xiaohu Ding and Evans, {David M.} and Puya Gharahkhani and Iglesias, {Adriana I.} and Toomas Haller and Xikun Han and Quan Hoang and Igo, {Robert P.} and Yip, {Shea Ping}",

year = "2020",

month = mar,

day = "19",

doi = "10.1038/s42003-020-0802-y",

language = "English",

volume = "3",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Fan, Q, Pozarickij, A, Tan, NYQ, Guo, X, Verhoeven, VJM, Vitart, V, Guggenheim, JA, Miyake, M, Tideman, JWL, Khawaja, AP, Zhang, L, MacGregor, S, Höhn, R, Chen, P, Biino, G, Wedenoja, J, Saffari, SE, Tedja, MS, Xie, J, Lanca, C, Wang, YX, Sahebjada, S, Mazur, J, Mirshahi, A, Martin, NG, Yazar, S, Pennell, CE, Yap, M, Haarman, AEG, Enthoven, CA, Polling, JR, Bailey-Wilson, JE, Veluchamy, AB, Burdon, KP, Campbell, H, Chen, LJ, Chew, EY, Craig, JE, Cumberland, PM, Deangelis, MM, Delcourt, C, Ding, X, Evans, DM, Gharahkhani, P, Iglesias, AI, Haller, T, Han, X, Hoang, Q, Igo, RP & Yip, SP 2020, 'Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error', Communications Biology, vol. 3, no. 1, 133. https://doi.org/10.1038/s42003-020-0802-y

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error. / Fan, Qiao; Pozarickij, Alfred; Tan, Nicholas Y.Q. et al.
In: Communications Biology, Vol. 3, No. 1, 133, 19.03.2020.

Research output: Journal article publication › Journal article › Academic research › peer-review

TY - JOUR

T1 - Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

AU - Fan, Qiao

AU - Pozarickij, Alfred

AU - Tan, Nicholas Y.Q.

AU - Guo, Xiaobo

AU - Verhoeven, Virginie J.M.

AU - Vitart, Veronique

AU - Guggenheim, Jeremy A.

AU - Miyake, Masahiro

AU - Tideman, J. Willem L.

AU - Khawaja, Anthony P.

AU - Zhang, Liang

AU - MacGregor, Stuart

AU - Höhn, René

AU - Chen, Peng

AU - Biino, Ginevra

AU - Wedenoja, Juho

AU - Saffari, Seyed Ehsan

AU - Tedja, Milly S.

AU - Xie, Jing

AU - Lanca, Carla

AU - Wang, Ya Xing

AU - Sahebjada, Srujana

AU - Mazur, Johanna

AU - Mirshahi, Alireza

AU - Martin, Nicholas G.

AU - Yazar, Seyhan

AU - Pennell, Craig E.

AU - Yap, Maurice

AU - Haarman, Annechien E.G.

AU - Enthoven, Clair A.

AU - Polling, Jan Roelof

AU - Bailey-Wilson, Joan E.

AU - Veluchamy, Amutha Barathi

AU - Burdon, Kathryn P.

AU - Campbell, Harry

AU - Chen, Li Jia

AU - Chew, Emily Y.

AU - Craig, Jamie E.

AU - Cumberland, Phillippa M.

AU - Deangelis, Margaret M.

AU - Delcourt, Cécile

AU - Ding, Xiaohu

AU - Evans, David M.

AU - Gharahkhani, Puya

AU - Iglesias, Adriana I.

AU - Haller, Toomas

AU - Han, Xikun

AU - Hoang, Quan

AU - Igo, Robert P.

AU - Yip, Shea Ping

PY - 2020/3/19

Y1 - 2020/3/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85086778879&partnerID=8YFLogxK

U2 - 10.1038/s42003-020-0802-y

DO - 10.1038/s42003-020-0802-y

M3 - Journal article

AN - SCOPUS:85086778879

SN - 2399-3642

VL - 3

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 133

ER -

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

Abstract

ASJC Scopus subject areas

More information

Other files and links

Fingerprint

Cite this