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

NEIGHBOR Consortium; Yi Lu; Veronique Vitart; Kathryn P Burdon; Chiea Chuen Khor; Yelena Bykhovskaya; Alireza Mirshahi; Alex W Hewitt; Demelza Koehn; Pirro G Hysi; Wishal D Ramdas; Tanja Zeller; Eranga N Vithana; Belinda K Cornes; Wan-Ting Tay; E Shyong Tai; Ching-Yu Cheng; Jianjun Liu; Jia-Nee Foo; Seang Mei Saw; Gudmar Thorleifsson; Kari Stefansson; David P Dimasi; Richard A Mills; Jenny Mountain; Wei Ang; René Hoehn; Virginie J M Verhoeven; Franz Grus; Roger Wolfs; Raphaële Castagne; Karl J Lackner; Henriët Springelkamp; Jian Yang; Fridbert Jonasson; Dexter Y L Leung; Li J Chen; Clement C Y Tham; Igor Rudan; Zoran Vatavuk; Caroline Hayward; Jane Gibson; Angela J Cree; Alex Macleod; Sarah Ennis; Ozren Polasek; Harry Campbell; James F Wilson; Ananth C Viswanathan; Brian Fleck; Alan F Wright

doi:10.1038/ng.2506

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

NEIGHBOR Consortium, Yi Lu, Veronique Vitart, Kathryn P Burdon, Chiea Chuen Khor, Yelena Bykhovskaya, Alireza Mirshahi, Alex W Hewitt, Demelza Koehn, Pirro G Hysi, Wishal D Ramdas, Tanja Zeller, Eranga N Vithana, Belinda K Cornes, Wan-Ting Tay, E Shyong Tai, Ching-Yu Cheng, Jianjun Liu, Jia-Nee Foo, Seang Mei SawGudmar Thorleifsson, Kari Stefansson, David P Dimasi, Richard A Mills, Jenny Mountain, Wei Ang, René Hoehn, Virginie J M Verhoeven, Franz Grus, Roger Wolfs, Raphaële Castagne, Karl J Lackner, Henriët Springelkamp, Jian Yang, Fridbert Jonasson, Dexter Y L Leung, Li J Chen, Clement C Y Tham, Igor Rudan, Zoran Vatavuk, Caroline Hayward, Jane Gibson, Angela J Cree, Alex Macleod, Sarah Ennis, Ozren Polasek, Harry Campbell, James F Wilson, Ananth C Viswanathan, Brian Fleck, Alan F Wright

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	155-163
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	2
Early online date	6 Jan 2013
DOIs	https://doi.org/10.1038/ng.2506
Publication status	Published - Feb 2013

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10.1038/ng.2506

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
Published in final edited form as: Nat Genet. Feb 2013; 45(2): 155–163. Published online Jan 6, 2013. doi: 10.1038/ng.2506
Accepted author manuscript, 1.2 MB

http://www.nature.com/ng/journal/v45/n2/full/ng.2506.html

Orkney Complex Disease Study ORCADES Cardiovascular Study
Wilson, J. (Principal Investigator), Campbell, H. (Co-investigator) & Wild, S. (Co-investigator)
UK central government bodies/local authorities, health and hospital authorities
1/04/09 → 31/12/12
Project: Research

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NEIGHBOR Consortium, 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., ... Wright, A. F. (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

@article{435f9c7e0d8242fbb0eec70f8cf5adce,

title = "Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus",

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.",

author = "\{NEIGHBOR Consortium\} and Yi Lu and Veronique Vitart and Burdon, \{Kathryn P\} and Khor, \{Chiea Chuen\} and Yelena Bykhovskaya and Alireza Mirshahi and Hewitt, \{Alex W\} and Demelza Koehn and Hysi, \{Pirro G\} and Ramdas, \{Wishal D\} and Tanja Zeller and Vithana, \{Eranga N\} and Cornes, \{Belinda K\} and Wan-Ting Tay and Tai, \{E Shyong\} and Ching-Yu Cheng and Jianjun Liu and Jia-Nee Foo and Saw, \{Seang Mei\} and Gudmar Thorleifsson and Kari Stefansson and Dimasi, \{David P\} and Mills, \{Richard A\} and Jenny Mountain and Wei Ang and Ren{\'e} Hoehn and Verhoeven, \{Virginie J M\} and Franz Grus and Roger Wolfs and Rapha{\"e}le Castagne and Lackner, \{Karl J\} and Henri{\"e}t Springelkamp and Jian Yang and Fridbert Jonasson and Leung, \{Dexter Y L\} and Chen, \{Li J\} and Tham, \{Clement C Y\} and Igor Rudan and Zoran Vatavuk and Caroline Hayward and Jane Gibson and Cree, \{Angela J\} and Alex Macleod and Sarah Ennis and Ozren Polasek and Harry Campbell and Wilson, \{James F\} and Viswanathan, \{Ananth C\} and Brian Fleck and Wright, \{Alan F\}",

year = "2013",

month = feb,

doi = "10.1038/ng.2506",

language = "English",

volume = "45",

pages = "155--163",

journal = "Nature Genetics",

publisher = "Nature Publishing Group",

number = "2",

}

NEIGHBOR Consortium, Lu, Y, Vitart, V, Burdon, KP, Khor, CC, Bykhovskaya, Y, Mirshahi, A, Hewitt, AW, Koehn, D, Hysi, PG, Ramdas, WD, Zeller, T, Vithana, EN, Cornes, BK, Tay, W-T, Tai, ES, Cheng, C-Y, Liu, J, Foo, J-N, Saw, SM, Thorleifsson, G, Stefansson, K, Dimasi, DP, Mills, RA, Mountain, J, Ang, W, Hoehn, R, Verhoeven, VJM, Grus, F, Wolfs, R, Castagne, R, Lackner, KJ, Springelkamp, H, Yang, J, Jonasson, F, Leung, DYL, Chen, LJ, Tham, CCY, Rudan, I, Vatavuk, Z, Hayward, C, Gibson, J, Cree, AJ, Macleod, A, Ennis, S, Polasek, O, Campbell, H , Wilson, JF, Viswanathan, AC, Fleck, B & Wright, AF 2013, 'Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus', Nature Genetics, vol. 45, no. 2, pp. 155-163. https://doi.org/10.1038/ng.2506

TY - JOUR

T1 - Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

AU - NEIGHBOR Consortium

AU - Lu, Yi

AU - Vitart, Veronique

AU - Burdon, Kathryn P

AU - Khor, Chiea Chuen

AU - Bykhovskaya, Yelena

AU - Mirshahi, Alireza

AU - Hewitt, Alex W

AU - Koehn, Demelza

AU - Hysi, Pirro G

AU - Ramdas, Wishal D

AU - Zeller, Tanja

AU - Vithana, Eranga N

AU - Cornes, Belinda K

AU - Tay, Wan-Ting

AU - Tai, E Shyong

AU - Cheng, Ching-Yu

AU - Liu, Jianjun

AU - Foo, Jia-Nee

AU - Saw, Seang Mei

AU - Thorleifsson, Gudmar

AU - Stefansson, Kari

AU - Dimasi, David P

AU - Mills, Richard A

AU - Mountain, Jenny

AU - Ang, Wei

AU - Hoehn, René

AU - Verhoeven, Virginie J M

AU - Grus, Franz

AU - Wolfs, Roger

AU - Castagne, Raphaële

AU - Lackner, Karl J

AU - Springelkamp, Henriët

AU - Yang, Jian

AU - Jonasson, Fridbert

AU - Leung, Dexter Y L

AU - Chen, Li J

AU - Tham, Clement C Y

AU - Rudan, Igor

AU - Vatavuk, Zoran

AU - Hayward, Caroline

AU - Gibson, Jane

AU - Cree, Angela J

AU - Macleod, Alex

AU - Ennis, Sarah

AU - Polasek, Ozren

AU - Campbell, Harry

AU - Wilson, James F

AU - Viswanathan, Ananth C

AU - Fleck, Brian

AU - Wright, Alan F

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

U2 - 10.1038/ng.2506

DO - 10.1038/ng.2506

M3 - Article

C2 - 23291589

VL - 45

SP - 155

EP - 163

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

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Orkney Complex Disease Study ORCADES Cardiovascular Study

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