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

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    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 languageEnglish
    Article number133
    Number of pages14
    JournalCommunications Biology
    Publication statusPublished - 19 Mar 2020

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


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