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

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., Lanca, C., Wang, Y. X., Sahebjada, S., Mazur, J., Mirshahi, A., Martin, N. G., Yazar, S., Pennell, C. E., Yap, M., Haarman, A. E. G., Enthoven, C. A., Polling, J. R., Bailey-Wilson, J. E., Veluchamy, A. B., Burdon, K. P., Campbell, H., Chen, L. J., Chew, E. Y., Craig, J. E., Cumberland, P. M., Deangelis, M. M., Delcourt, C., Ding, X., Evans, D. M., Gharahkhani, P., Iglesias, A. I., Haller, T., Han, X., Hoang, Q., Igo, R. P., Iyengar, S. K., Kähönen, M., Kaprio, J., Klein, B. E., Klein, R., Lass, J. H., Lee, K., Lehtimäki, T., Lewis, D. D., Li, Q., Li, S. M., Lyytikäinen, L. P., Meguro, A., Metspalu, A., Middlebrooks, C. D., Mizuki, N., Musolf, A. M., Nickels, S., Oexle, K., Pang, C. P., Paterson, A. D., Rahi, J. S., Raitakari, O., Rudan, I., Stambolian, D., Simpson, C. L., Wang, N., Bin Wei, W., Williams, K. M., Wilson, J. F., Wojciechowski, R., Yamashiro, K., Yam, J. C. S., Zhou, X., Aslam, T., Barman, S. A., Barrett, J. H., Bishop, P., Blows, P., Bunce, C., Carare, R. O., Chakravarthy, U., Chan, M., Chua, S. Y. L., Crabb, D. P. ORCID: 0000-0001-8754-3902, Cumberland, P. M., Day, A., Desai, P., Dhillon, B., Dick, A. D. & Egan, C. (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(1), 133. doi: 10.1038/s42003-020-0802-y


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.

Publication Type: Article
Additional Information: 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, visit
Publisher Keywords: Corneal diseases, Genetic predisposition to disease, Genome-wide association studies
Subjects: R Medicine > RE Ophthalmology
Departments: School of Health & Psychological Sciences > Optometry & Visual Sciences
Text - Published Version
Available under License Creative Commons Attribution.

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