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; The CREAM Consortium; Joan E. Bailey-Wilson; Amutha Barathi Veluchamy; Kathryn P. Burdon; Harry Campbell; Li Jia Chen; Emily Y. Chew; Jamie E. Craig; Philippa 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; Sudha K. Iyengar; Mika Kähönen; Jaakko Kaprio; Barbara E. Klein; Ronald Klein; Jonathan H. Lass; Kris Lee; Terho Lehtimäki; Deyana D. Lewis; Qing Li; Shi Ming Li; Leo Pekka Lyytikäinen; Akira Meguro; Andres Metspalu; Candace D. Middlebrooks; Nobuhisa Mizuki; Anthony M. Musolf; Stefan Nickels; Konrad Oexle; Chi Pui Pang; Andrew D. Paterson; Jugnoo S. Rahi; Olli Raitakari; Igor Rudan; Dwight Stambolian; Claire L. Simpson; Ningli Wang; Wen Bin Wei; Katie Williams; James F. Wilson; UK Biobank Eye and Vision Consortium; Jenny H. Barrett; Paul Bishop; Peter Blows; Catey Bunce; Roxana O. Carare; Usha Chakravarthy; Michelle Chan; Sharon Y.L. Chua; David P. Crabb; Philippa M. Cumberland; Alexander Day; Parul Desai; Bal Dhillon; Andrew D. Dick; Cathy Egan; Sarah Ennis; Marcus Fruttiger; John E.J. Gallacher; David F. Garway-Heath; Jane Gibson; Dan Gore; Alison Hardcastle; Simon P. Harding; Ruth E. Hogg; Pearse A. Keane; Sir Peng T. Khaw; Gerassimos Lascaratos; Andrew J. Lotery; Tom Macgillivray; Sarah Mackie; Keith Martin; Michelle McGaughey; Bernadette McGuinness; Gareth J. McKay; Martin McKibbin; Danny Mitry; Tony Moore; James E. Morgan; Zaynah A. Muthy; Eoin O’Sullivan; Chris G. Owen; Praveen Patel; Euan Paterson; Tunde Peto; Axel Petzold; Jugnoo S. Rahi; Alicja R. Rudnikca; Jay Self; Sobha Sivaprasad; David Steel; Irene Stratton; Nicholas Strouthidis; Cathie Sudlow; Dhanes Thomas; Emanuele Trucco; Adnan Tufail; Stephen A. Vernon; Ananth C. Viswanathan; Katie Williams; Jayne V. Woodside; Max M. Yates; Jennifer Yip; Yalin Zheng; 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 Pärssinen; 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

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, The CREAM Consortium , Joan E. Bailey-Wilson, Amutha Barathi Veluchamy, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Emily Y. Chew, Jamie E. Craig, Philippa 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, Sudha K. Iyengar, Mika Kähönen, Jaakko Kaprio, Barbara E. Klein, Ronald Klein, Jonathan H. Lass, Kris Lee, Terho Lehtimäki, Deyana D. Lewis, Qing Li, Shi Ming Li, Leo Pekka Lyytikäinen, Akira Meguro, Andres Metspalu, Candace D. Middlebrooks, Nobuhisa Mizuki, Anthony M. Musolf, Stefan Nickels, Konrad Oexle, Chi Pui Pang, Andrew D. Paterson, Jugnoo S. Rahi, Olli Raitakari, Igor Rudan, Dwight Stambolian, Claire L. Simpson, Ningli Wang, Wen Bin Wei, Katie Williams, James F. Wilson, UK Biobank Eye and Vision Consortium, Jenny H. Barrett, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Y.L. Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Marcus Fruttiger, John E.J. Gallacher, David F. Garway-Heath, Jane Gibson, Dan Gore, Alison Hardcastle, Simon P. Harding, Ruth E. Hogg, Pearse A. Keane, Sir Peng T. Khaw, Gerassimos Lascaratos, Andrew J. Lotery, Tom Macgillivray, Sarah Mackie, Keith Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, James E. Morgan, Zaynah A. Muthy, Eoin O’Sullivan, Chris G. Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnikca, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Stephen A. Vernon, Ananth C. Viswanathan, Katie Williams, Jayne V. Woodside, Max M. Yates, Jennifer Yip, Yalin Zheng, 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 Pärssinen, 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

Research output: Contribution to journal › Review article › peer-review

11 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
Number of pages	14
Journal	Communications Biology
Volume	3
DOIs	https://doi.org/10.1038/s42003-020-0802-y
Publication status	Published - 19 Mar 2020

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.

Keywords

corneal diseases
Genome-wide association studies
genetic predisposition to disease
myopia
corneal curvature
visual impairment

Access to Document

10.1038/s42003-020-0802-yLicence: CC BY

Published versionFinal published version, 2.25 MBLicence: CC BY

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., ... Cheng, C. Y. (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, [133]. https://doi.org/10.1038/s42003-020-0802-y

@article{b323cf2a81ea4edeb684dd26bab80e9e,

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.",

keywords = "corneal diseases, Genome-wide association studies, genetic predisposition to disease, myopia, corneal curvature, visual impairment",

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 {The CREAM Consortium} 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, {Philippa 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 Iyengar, {Sudha K.} and Mika K{\"a}h{\"o}nen and Jaakko Kaprio and Klein, {Barbara E.} and Ronald Klein and Lass, {Jonathan H.} and Kris Lee and Terho Lehtim{\"a}ki and Lewis, {Deyana D.} and Qing Li and Li, {Shi Ming} and Lyytik{\"a}inen, {Leo Pekka} and Akira Meguro and Andres Metspalu and Middlebrooks, {Candace D.} and Nobuhisa Mizuki and Musolf, {Anthony M.} and Stefan Nickels and Konrad Oexle and Pang, {Chi Pui} and Paterson, {Andrew D.} and Rahi, {Jugnoo S.} and Olli Raitakari and Igor Rudan and Dwight Stambolian and Simpson, {Claire L.} and Ningli Wang and {Bin Wei}, Wen and Katie Williams and Wilson, {James F.} and Kenji Yamashiro and Robert Wojciechowski and Yam, {Jason C.S.} and Xiangtian Zhou and {UK Biobank Eye and Vision Consortium} 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 Marcus Fruttiger and Gallacher, {John E.J.} and Garway-Heath, {David F.} and Jane Gibson and Dan Gore and Alison Hardcastle and Harding, {Simon P.} and Hogg, {Ruth E.} and Keane, {Pearse A.} and Khaw, {Sir Peng T.} and Gerassimos Lascaratos and Lotery, {Andrew J.} 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{\textquoteright}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 Katie Williams and Woodside, {Jayne V.} and Yates, {Max M.} and Jennifer Yip and Yalin Zheng and Hewitt, {Alex W.} and Jaddoe, {Vincent W.V.} and {van Duijn}, {Cornelia M.} and Caroline Hayward and Ozren Polasek and Tai, {E. Shyong} 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{\"a}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 Wong, {Tien Yin} and Klaver, {Caroline C.W.} and Saw, {Seang Mei} and Baird, {Paul N.} and Cheng, {Ching Yu}",

note = "Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.",

year = "2020",

month = mar,

day = "19",

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

language = "English",

volume = "3",

journal = "Communications Biology",

issn = "2399-3642",

}

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, The CREAM Consortium , 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, Iyengar, SK, Kähönen, M, Kaprio, J, Klein, BE, Klein, R, Lass, JH, Lee, K, Lehtimäki, T, Lewis, DD, Li, Q, Li, SM, Lyytikäinen, LP, Meguro, A, Metspalu, A, Middlebrooks, CD, Mizuki, N, Musolf, AM, Nickels, S, Oexle, K, Pang, CP, Paterson, AD, Rahi, JS, Raitakari, O, Rudan, I, Stambolian, D, Simpson, CL, Wang, N, Bin Wei, W, Williams, K, Wilson, JF, UK Biobank Eye and Vision Consortium, Barrett, JH, Bishop, P, Blows, P, Bunce, C, Carare, RO, Chakravarthy, U, Chan, M, Chua, SYL, Crabb, DP, Cumberland, PM, Day, A, Desai, P, Dhillon, B, Dick, AD, Egan, C, Ennis, S, Fruttiger, M, Gallacher, JEJ, Garway-Heath, DF, Gibson, J, Gore, D, Hardcastle, A, Harding, SP, Hogg, RE, Keane, PA, Khaw, SPT, Lascaratos, G, Lotery, AJ, Macgillivray, T, Mackie, S, Martin, K, McGaughey, M, McGuinness, B, McKay, GJ, McKibbin, M, Mitry, D, Moore, T, Morgan, JE, Muthy, ZA, O’Sullivan, E, Owen, CG, Patel, P, Paterson, E, Peto, T, Petzold, A, Rahi, JS, Rudnikca, AR, Self, J, Sivaprasad, S, Steel, D, Stratton, I, Strouthidis, N, Sudlow, C, Thomas, D, Trucco, E, Tufail, A, Vernon, SA, Viswanathan, AC, Williams, K, Woodside, JV, Yates, MM, Yip, J, Zheng, Y, Hewitt, AW, Jaddoe, VWV, van Duijn, CM, Hayward, C, Polasek, O, Tai, ES, Yoshikatsu, H, Hysi, PG, Young, TL, Tsujikawa, A, Wang, JJ, Mitchell, P, Pfeiffer, N, Pärssinen, O, Foster, PJ, Fossarello, M, Yip, SP, Williams, C, Hammond, CJ, Jonas, JB, He, M, Mackey, DA, Wong, TY, Klaver, CCW, Saw, SM, Baird, PN & Cheng, CY 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 - 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 - The CREAM Consortium

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, Philippa 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 - Iyengar, Sudha K.

AU - Kähönen, Mika

AU - Kaprio, Jaakko

AU - Klein, Barbara E.

AU - Klein, Ronald

AU - Lass, Jonathan H.

AU - Lee, Kris

AU - Lehtimäki, Terho

AU - Lewis, Deyana D.

AU - Li, Qing

AU - Li, Shi Ming

AU - Lyytikäinen, Leo Pekka

AU - Meguro, Akira

AU - Metspalu, Andres

AU - Middlebrooks, Candace D.

AU - Mizuki, Nobuhisa

AU - Musolf, Anthony M.

AU - Nickels, Stefan

AU - Oexle, Konrad

AU - Pang, Chi Pui

AU - Paterson, Andrew D.

AU - Rahi, Jugnoo S.

AU - Raitakari, Olli

AU - Rudan, Igor

AU - Stambolian, Dwight

AU - Simpson, Claire L.

AU - Wang, Ningli

AU - Bin Wei, Wen

AU - Williams, Katie

AU - Wilson, James F.

AU - Yamashiro, Kenji

AU - Wojciechowski, Robert

AU - Yam, Jason C.S.

AU - Zhou, Xiangtian

AU - UK Biobank Eye and Vision Consortium

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 - Fruttiger, Marcus

AU - Gallacher, John E.J.

AU - Garway-Heath, David F.

AU - Gibson, Jane

AU - Gore, Dan

AU - Hardcastle, Alison

AU - Harding, Simon P.

AU - Hogg, Ruth E.

AU - Keane, Pearse A.

AU - Khaw, Sir Peng T.

AU - Lascaratos, Gerassimos

AU - Lotery, Andrew J.

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, Katie

AU - Woodside, Jayne V.

AU - Yates, Max M.

AU - Yip, Jennifer

AU - Zheng, Yalin

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 - Pärssinen, 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

N1 - Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.

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.

KW - corneal diseases

KW - Genome-wide association studies

KW - genetic predisposition to disease

KW - myopia

KW - corneal curvature

KW - visual impairment

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

UR - http://purl.org/au-research/grants/NHMRC/572613

UR - http://purl.org/au-research/grants/NHMRC/1021105

U2 - 10.1038/s42003-020-0802-y

DO - 10.1038/s42003-020-0802-y

M3 - Review article

AN - SCOPUS:85086778879

VL - 3

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

M1 - 133

ER -

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

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