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, Véronique 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 Lança, 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 Cumberland, Margaret M. DeAngelis, Cécile Delcourt, Xiaohu Ding, David M. Evans, Puya Gharahkhani, Adriana I. Iglesias, Toomas Haller, Xikun Han, Quan V. Hoang, Robert P. Igo, Sudha K. Iyengar, Mika Kähönen, Jaakko Kaprio, Ronald Klein, Ronald Klein, Jonathan H. Lass, K. Lee, Terho Lehtimäki, Deyana 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 T. Raitakari, Igor Rudan, Dwight Stambolian, Claire L. Simpson, Ningli Wang, Wen Bin Wei, Katie Williams, James F. Wilson, Robert Wojciechowski, Kenji Yamashiro, Jason C. Yam, Xiangtian Zhou, Tariq Aslam, Sarah Barman, Jenny H. Barrett, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan
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.