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

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
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
1061-4036
155-163
Lu, Yi
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Vitart, Veronique
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Burdon, Kathryn P.
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Khor, Chiea Chuen
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Bykhovskaya, Yelena
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Mirshahi, Alireza
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Hewitt, Alex W.
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Koehn, Demelza
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Hysi, Pirro G.
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Ramdas, Wishal D.
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Zeller, Tanja
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Vithana, Eranga N.
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Cornes, Belinda K.
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Tay, Wan-Ting
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Lotery, Andrew J.
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Hammond, Christopher J.
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van Duijn, Cornelia M.
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Hauser, Michael A.
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Ramdas, Wishal D.
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Ang, Wei
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Hoehn, René
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Verhoeven, Virginie J.M.
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Wolfs, Roger
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Castagne, Raphaële
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Siscovick, David
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Rotter, Jerome I.
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Haines, Jonathan L
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Lu, Yi, Vitart, Veronique, Burdon, Kathryn P., Khor, Chiea Chuen, Bykhovskaya, Yelena, Mirshahi, Alireza, Hewitt, Alex W., Koehn, Demelza, Hysi, Pirro G., Ramdas, Wishal D., Zeller, Tanja, Vithana, Eranga N., Cornes, Belinda K., Tay, Wan-Ting, Tai, E Shyong, Cheng, Ching-Yu, Liu, Jianjun, Foo, Jia-Nee, Saw, Seang Mei, Thorleifsson, Gudmar, Stefansson, Kari, Dimasi, David P., Mills, Richard A., Mountain, Jenny, Ang, Wei, Hoehn, René, Verhoeven, Virginie J.M., Grus, Franz, Wolfs, Roger, Castagne, Raphaële, Lackner, Karl J., Springelkamp, Henriët, Yang, Jian, Jonasson, Fridbert, Leung, Dexter Y.L., Chen, Li J, Tham, Clement C.Y., Rudan, Igor, Vatavuk, Zoran, Hayward, Caroline, Gibson, Jane, Cree, Angela J., MacLeod, Alex, Ennis, Sarah, Polasek, Ozren, Campbell, Harry, Wilson, James F., Viswanathan, Ananth C., Fleck, Brian, Li, Xiaohui, Siscovick, David, Taylor, Kent D, Rotter, Jerome I., Yazar, Seyhan, Ulmer, Megan, Li, Jun, Yaspan, Brian L., Ozel, Ayse B., Richards, Julia E., Moroi, Sayoko E., Haines, Jonathan L, Kang, Jae H., Pasquale, Louis R., Allingham, R. Rand, Ashley-Koch, Allison, Mitchell, Paul, Wang, Jie Jin, Wright, Alan F., Pennell, Craig, Spector, Timothy D., Young, Terri L., Klaver, Caroline C.W., Martin, Nicholas G., Montgomery, Grant W., Anderson, Michael G., Aung, Tin, Willoughby, Colin E., Wiggs, Janey L., Pang, Chi P., Thorsteinsdottir, Unnur, Lotery, Andrew J., Hammond, Christopher J., van Duijn, Cornelia M., Hauser, Michael A., Rabinowitz, Yaron S., Pfeiffer, Norbert, Mackey, David A., Craig, Jamie E., Macgregor, Stuart and Wong, Tien Y. (2013) Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature Genetics, 45 (2), 155-163. (doi:10.1038/ng.2506). (PMID:23291589)

Record type: Article

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

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More information

e-pub ahead of print date: 6 January 2013
Published date: February 2013
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 346778
URI: http://eprints.soton.ac.uk/id/eprint/346778
DOI: doi:10.1038/ng.2506
ISSN: 1061-4036
PURE UUID: 239ef414-c476-48ee-b409-7ecb2f4e0376
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Angela J. Cree: ORCID iD orcid.org/0000-0002-1987-8900
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 09 Jan 2013 14:18
Last modified: 15 Mar 2024 03:24

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Contributors

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

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