Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
Authors: Fan Qiao , Pozarickij Alfred , Tan Nicholas Y. Q. , Guo Xiaobo , Verhoeven Virginie J. M. , Vitart Veronique , Guggenheim Jeremy A. , Miyake Masahiro , Tideman J. Willem L. , Khawaja Anthony P. , Zhang Liang , MacGregor Stuart , Höhn René , Chen Peng , Biino Ginevra , Wedenoja Juho , Saffari Seyed Ehsan , Tedja Milly S. , Xie Jing , Lanca Carla , Wang Ya Xing , Sahebjada Srujana , Mazur Johanna , Mirshahi Alireza , Martin Nicholas G. , Yazar Seyhan , Pennell Craig E. , Yap Maurice , Haarman Annechien E. G. , Enthoven Clair A. , Polling JanRoelof ,   Consortium for Refractive Error and Myopia (CREAM), Bailey-Wilson Joan E. , Veluchamy Amutha Barathi , Burdon Kathryn P. , Campbell Harry , Chen Li Jia , Chew Emily Y. , Craig Jamie E. , Cumberland Phillippa M. , Deangelis Margaret M. , Delcourt Cécile , Ding Xiaohu , Evans David M. , Gharahkhani Puya , Iglesias Adriana I. , Haller Toomas , Han Xikun , Hoang Quan , Igo Robert P. , Iyengar Sudha K. , Kähönen Mika , Kaprio Jaakko , Klein Barbara E. , Klein Ronald , Lass Jonathan H. , Lee Kris , Lehtimäki Terho , Lewis Deyana D. , Li Qing , Li Shi-Ming , Lyytikäinen Leo-Pekka , Meguro Akira , Metspalu Andres , Middlebrooks Candace D. , Mizuki Nobuhisa , Musolf Anthony M. , Nickels Stefan , Oexle Konrad , Pang Chi Pui , Paterson Andrew D. , Rahi Jugnoo S. , Raitakari Olli , Rudan Igor , Stambolian Dwight , Simpson Claire L. , Wang Ningli , Bin Wei Wen , Williams Katie M. , Wilson James F. , Wojciechowski Robert , Yamashiro Kenji , Yam Jason C. S. , Zhou Xiangtian ,   UK Biobank Eye and Vision Consortium, Aslam Tariq , Barman Sarah A. , Barrett Jenny H. , Bishop Paul , Blows Peter , Bunce Catey , Carare Roxana O. , Chakravarthy Usha , Chan Michelle , Chua Sharon Y. L. , Crabb David P. , Cumberland Philippa M. , Day Alexander , Desai Parul , Dhillon Bal , Dick Andrew D. , Egan Cathy , Ennis Sarah , Fruttiger Marcus , Gallacher John E. J. , Garway-Heath David F. , Gibson Jane , Gore Dan , Hardcastle Alison , Harding Simon P. , Hogg Ruth E. , Keane Pearse A. , Khaw Sir Peng T. , Lascaratos Gerassimos , Lotery Andrew J. , Macgillivray Tom , Mackie Sarah , Martin Keith , McGaughey Michelle , McGuinness Bernadette , McKay Gareth J. , McKibbin Martin , Mitry Danny , Moore Tony , Morgan James E. , Muthy Zaynah A. , O’Sullivan Eoin , Owen Chris G. , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Rahi Jugnoo S. , Rudnikca Alicja R. , Self Jay , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Thomas Dhanes , Trucco Emanuele , Tufail Adnan , Vernon Stephen A. , Viswanathan Ananth C. , Williams Katie , Woodside Jayne V. , Yates Max M. , Yip Jennifer , Zheng Yalin , Hewitt Alex W. , Jaddoe Vincent W. V. , van Duijn Cornelia M. , Hayward Caroline , Polasek Ozren , Tai E-Shyong , Yoshikatsu Hosoda , Hysi Pirro G. , Young Terri L. , Tsujikawa Akitaka , Wang Jie Jing , Mitchell Paul , Pfeiffer Norbert , Pärssinen Olavi , Foster Paul J. , Fossarello Maurizio , Yip Shea Ping , Williams Cathy , Hammond Christopher J. , Jonas Jost B. , He Mingguang , Mackey David A. , Wong Tien-Yin , Klaver Caroline C. W. , Saw Seang-Mei , Baird Paul N. , Cheng Ching-Yu 
Published: March 2020

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/FBLN2rs2630445,RBP3rs11204213); 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.