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

Annechien E. G. Haarman; Clair A. Enthoven; JanRoelof Polling; Consortium for Refractive Error and Myopia (CREAM); UK Biobank Eye and Vision Consortium; Sarah A. Barman; Alex W. Hewitt; Vincent W. V. Jaddoe; Cornelia M. van Duijn; Caroline Hayward; Ozren Polasek; E-Shyong Tai; Hosoda Yoshikatsu; Pirro G. Hysi; Terri L. Young; Akitaka Tsujikawa; Jie Jing Wang; Paul Mitchell; Norbert Pfeiffer; Olavi P├ñrssinen; Paul J. Foster; Maurizio Fossarello; Shea Ping Yip; Cathy Williams; Christopher J. Hammond; Jost B. Jonas; Mingguang He; David A. Mackey; Tien-Yin Wong; Caroline C. W. Klaver; Seang-Mei Saw; Paul N. Baird; Ching-Yu Cheng; 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; 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; Ren├® H├Âhn; Peng Chen; Ginevra Biino; Juho Wedenoja

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

Annechien E. G. Haarman
, Clair A. Enthoven
, JanRoelof Polling
, Consortium for Refractive Error and Myopia (CREAM)
, UK Biobank Eye and Vision Consortium
, Sarah A. Barman
, Alex W. Hewitt
, Vincent W. V. Jaddoe
, Cornelia M. van Duijn
, Caroline Hayward
, Ozren Polasek
, E-Shyong Tai
, Hosoda Yoshikatsu
, Pirro G. Hysi
, Terri L. Young
, Akitaka Tsujikawa
, Jie Jing Wang
, Paul Mitchell
, Norbert Pfeiffer
, Olavi P├ñrssinen

Paul J. Foster, Maurizio Fossarello, Shea Ping Yip, Cathy Williams, Christopher J. Hammond, Jost B. Jonas, Mingguang He, David A. Mackey, Tien-Yin Wong, Caroline C. W. Klaver, Seang-Mei Saw, Paul N. Baird, Ching-Yu Cheng, 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, 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, Ren├® H├Âhn, Peng Chen, Ginevra Biino, Juho Wedenoja

Research output: Contribution to journal › Article › peer-review

Abstract

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
Early online date	19 Mar 2020
DOIs	https://doi.org/10.1038/s42003-020-0802-y
Publication status	Published - 19 Mar 2020

Bibliographical note

Note: A full list of funding information and acknowledgements by individual study can be found in the Supplementary Note (available via the DOI).

Keywords

Biological sciences

Access to Document

10.1038/s42003-020-0802-y

Barman-S-48403-VoRFinal published version, 2.25 MBLicence: CC BY

https://doi.org/10.1038/s42003-020-0802-y

Cite this

Haarman, A. E. G., Enthoven, C. A., Polling, J., Consortium for Refractive Error and Myopia (CREAM), UK Biobank Eye and Vision Consortium, Barman, S. A., Hewitt, A. W., Jaddoe, V. W. V., van Duijn, C. M., Hayward, C., Polasek, O., Tai, E.-S., Yoshikatsu, H., Hysi, P. G., Young, T. L., Tsujikawa, A., Wang, J. J., Mitchell, P., Pfeiffer, N., ... Wedenoja, J. (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, Article 133. https://doi.org/10.1038/s42003-020-0802-y

@article{fb2986f4b9eb4832b4b5d1d9ff2ea3b4,

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

abstract = "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.",

keywords = "Biological sciences",

author = "Haarman, \{Annechien E. G.\} and Enthoven, \{Clair A.\} and JanRoelof Polling and \{Consortium for Refractive Error and Myopia (CREAM)\} and \{UK Biobank Eye and Vision Consortium\} and Barman, \{Sarah A.\} and Hewitt, \{Alex W.\} and Jaddoe, \{Vincent W. V.\} and \{van Duijn\}, \{Cornelia M.\} and Caroline Hayward and Ozren Polasek and E-Shyong Tai and Hosoda Yoshikatsu and Hysi, \{Pirro G.\} and Young, \{Terri L.\} and Akitaka Tsujikawa and Wang, \{Jie Jing\} and Paul Mitchell and Norbert Pfeiffer and Olavi P├{\~n}rssinen and Foster, \{Paul J.\} and Maurizio Fossarello and Yip, \{Shea Ping\} and Cathy Williams and Hammond, \{Christopher J.\} and Jonas, \{Jost B.\} and Mingguang He and Mackey, \{David A.\} and Tien-Yin Wong and Klaver, \{Caroline C. W.\} and Seang-Mei Saw and Baird, \{Paul N.\} and Ching-Yu Cheng 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 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├{\textregistered} H├{\^A}hn and Peng Chen and Ginevra Biino and Juho Wedenoja",

note = "Note: A full list of funding information and acknowledgements by individual study can be found in the Supplementary Note (available via the DOI).",

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",

}

Haarman, AEG, Enthoven, CA, Polling, J, Consortium for Refractive Error and Myopia (CREAM), UK Biobank Eye and Vision Consortium, , Barman, SA, Hewitt, AW, Jaddoe, VWV, van Duijn, CM, Hayward, C, Polasek, O, Tai, E-S, Yoshikatsu, H, Hysi, PG, Young, TL, Tsujikawa, A, Wang, JJ, Mitchell, P, Pfeiffer, N, P├ñrssinen, O, Foster, PJ, Fossarello, M, Yip, SP, Williams, C, Hammond, CJ, Jonas, JB, He, M, Mackey, DA, Wong, T-Y, Klaver, CCW, Saw, S-M, Baird, PN, Cheng, C-Y, Saffari, SE, Tedja, MS, Xie, J, Lanca, C, Wang, YX, Sahebjada, S, Mazur, J, Mirshahi, A, Martin, NG, Yazar, S, Pennell, CE, Yap, M, Fan, Q, Pozarickij, A, Tan, NYQ, Guo, X, Verhoeven, VJM, Vitart, V, Guggenheim, JA, Miyake, M, Tideman, JWL, Khawaja, AP, Zhang, L, MacGregor, S, H├Âhn, R, Chen, P, Biino, G & Wedenoja, J 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, 133. https://doi.org/10.1038/s42003-020-0802-y

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 - Haarman, Annechien E. G.

AU - Enthoven, Clair A.

AU - Polling, JanRoelof

AU - Consortium for Refractive Error and Myopia (CREAM), null

AU - UK Biobank Eye and Vision Consortium, null

AU - Barman, Sarah A.

AU - Hewitt, Alex W.

AU - Jaddoe, Vincent W. V.

AU - van Duijn, Cornelia M.

AU - Hayward, Caroline

AU - Polasek, Ozren

AU - Tai, E-Shyong

AU - Yoshikatsu, Hosoda

AU - Hysi, Pirro G.

AU - Young, Terri L.

AU - Tsujikawa, Akitaka

AU - Wang, Jie Jing

AU - Mitchell, Paul

AU - Pfeiffer, Norbert

AU - P├ñrssinen, Olavi

AU - Foster, Paul J.

AU - Fossarello, Maurizio

AU - Yip, Shea Ping

AU - Williams, Cathy

AU - Hammond, Christopher J.

AU - Jonas, Jost B.

AU - He, Mingguang

AU - Mackey, David A.

AU - Wong, Tien-Yin

AU - Klaver, Caroline C. W.

AU - Saw, Seang-Mei

AU - Baird, Paul N.

AU - Cheng, Ching-Yu

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 - 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 - H├Âhn, Ren├®

AU - Chen, Peng

AU - Biino, Ginevra

AU - Wedenoja, Juho

N1 - Note: A full list of funding information and acknowledgements by individual study can be found in the Supplementary Note (available via the DOI).

PY - 2020/3/19

Y1 - 2020/3/19

N2 - 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.

AB - 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.

KW - Biological sciences

U2 - 10.1038/s42003-020-0802-y

DO - 10.1038/s42003-020-0802-y

M3 - Article

SN - 2399-3642

VL - 3

JO - Communications Biology

JF - Communications Biology

M1 - 133

ER -

Haarman AEG, Enthoven CA, Polling J, Consortium for Refractive Error and Myopia (CREAM), UK Biobank Eye and Vision Consortium , Barman SA et al. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error. Communications Biology. 2020 Mar 19;3:133. Epub 2020 Mar 19. 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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this