Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

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Lu, Yi
Vitart, Veronique
Burdon, Kathryn Penelope
Khor, Chiea Chuen
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Nature Publishing Group
Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
The author manuscript of this article is open access and is freely available online at PubMed Central <>
Genetics, Central corneal thickness, Glaucoma, Keratoconus
Lu, Y., Vitart, V., Burdon, K. P., Khor, C. C., Bykhovskaya, Y., Mirshahi, A., Hewitt, A. W., Koehn, D., Hysi, P. G., Ramdas, W. D., Zeller, T., Vithana, E. N., Cornes, B. K., Tay, W. T., Tai, E. S., Cheng, C. Y., Liu, J., Foo, J. N., Saw, S. M., Thorleifsson, G., Stefansson, K., Dimasi, D. P., Mills, R. A., Mountain, J., Ang, W., Hoehn, R., Verhoeven, V. J. M., Grus, F., Wolfs, R., Castagne, R., Lackner, K. J., Springelkamp, H., Yang, J., Jonasson, F., Leung, D. Y. L., Chen, L. J., Tham, C. C. Y., Rudan, I., Vatavuk, Z., Hayward, C., Gibson, J., Cree, A. J., MacLeod, A., Ennis, S., Polasek, O., Campbell, H., Wilson, J. F., Viswanathan, A. C., Fleck, B., Li, X., Siscovick, D., Taylor, K. D., Rotter, J. I., Yazar, S., Ulmer, M., Li, J., Yaspan, B. L., Ozel, A. B., Richards, J. E., Moroi, S. E., Haines, J. L., Kang, J. H., Pasquale, L. R., Allingham, R. R., Ashley-Koch, A., Mitchell, P., Wang, J. J., Wright, A. F., Pennell, C., Spector, T. D., Young, T. L., Klaver, C. C. W., Martin, N. G., Montgomery, G. W., Anderson, M. G., Aung, T., Willoughby, C. E., Wiggs, J. L., Pang, C. P., Thorsteinsdottir, U., Lotery, A. J., Hammond, C. J., Van Duijn, C. M., Hauser, M. A., Rabinowitz, Y. S., Pfeiffer, N., MacKey, D. A., Craig, J. E., MacGregor, S., Wong, T. Y. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature Genetics 2013;45(2):155-63. IF-35.20