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

Yi Lu, Veronique Vitart, Kathryn Burdon, Chiea-Chuen Khor, Yelena Bykhovskaya, Alireza Mirshahi, Alex Hewitt, Demelza Koehn, Pirro Hysi, Wishal Ramdas, Tanja Zeller, Eranga Vithana, Belinda Cornes, Wan-Ting Tay, E-Shyong Tai, Ching-Yu Cheng, Jianjun Liu, Jia-Nee Foo, Seang-Mei Saw, Gudmar ThorleifssonKari Stefansson, David Dimasi, Richard Mills, Jenny Mountain, Wei Ang, René Hoehn, Virginie Verhoeven, Franz Grus, Roger Wolfs, Raphaële Castagne, Karl Lackner, Hanriët Springelkamp, Jian Yang, Fridbert Jonasson, Dexter Leung, Li Chen, Clement Tham, Igor Rudan, Zoran Vatavuk, Caroline Hayward, Jane Gibson, Angela Cree, Alex Macleod, Sarah Ennis, Ozren Polasek, Harry Campbell, James Wilson, Ananth Viswanathan, Brian Fleck, Xiaohui Li, David Siscovick, Kent Taylor, Jerome Rotter, Seyhan Yazar, Megan Ulmer, Jun Li, Brian Yaspan, Ayse Ozel, Julia Richards, Sayoko Moroi, Jonathan Haines, Jae Kang, Louis Pasquale, R Allingham, Allison Ashely-Koch, Paul Mitchell, Jie Jin Wang, Alan Wright, Craig Pennell, Timothy Spector, Terri Young, Caroline Klaver, Nicholas Martin, Grant Montgomery, Michael Anderson, Tin Aung, Colin Willoughby, Janey Wiggs, Chi Pui Pang, Unnur Thorsteinsdottir, Andrew Lotery, Christopher Hammond, Cornelia van Duijn, Michael Hauser, Yaron Rabinowitz, Norbert Pfeiffer, David Mackey, Jamie Craig, Stuart Macgregor, Tien Wong

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    164 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)155-163
    Number of pages9
    JournalNature Genetics
    Volume45
    Issue number2
    DOIs
    Publication statusPublished - 2013

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  • Cite this

    Lu, Y., Vitart, V., Burdon, K., Khor, C-C., Bykhovskaya, Y., Mirshahi, A., Hewitt, A., Koehn, D., Hysi, P., Ramdas, W., Zeller, T., Vithana, E., Cornes, B., Tay, W-T., Tai, E-S., Cheng, C-Y., Liu, J., Foo, J-N., Saw, S-M., ... Wong, T. (2013). Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature Genetics, 45(2), 155-163. https://doi.org/10.1038/ng.2506