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

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; Xiaohui Li; David Siscovick; Kent D. Taylor; Jerome I. Rotter; Seyhan Yazar; Megan Ulmer; Jun Li; Brian L. Yaspan; Ayse B. Ozel; Julia E. Richards; Sayoko E. Moroi; Jonathan L. Haines; Jae H. Kang; Louis R. Pasquale; R. Rand Allingham; Allison Ashley-Koch; Paul Mitchell; Jie Jin Wang; Alan F. Wright; Craig Pennell; Timothy D. Spector; Terri L. Young; Caroline C.W. Klaver; Nicholas G. Martin; Grant W. Montgomery; Michael G. Anderson; Tin Aung; Colin E. Willoughby; Janey L. Wiggs; Chi P. Pang; Unnur Thorsteinsdottir; Andrew J. Lotery; Christopher J. Hammond; Cornelia M. Van Duijn; Michael A. Hauser; Yaron S. Rabinowitz; Norbert Pfeiffer; David A. MacKey; Jamie E. Craig; Stuart MacGregor; Tien Y. Wong

doi:10.1038/ng.2506

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

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 ThorleifssonKari 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, Xiaohui Li, David Siscovick, Kent D. Taylor, Jerome I. Rotter, Seyhan Yazar, Megan Ulmer, Jun Li, Brian L. Yaspan, Ayse B. Ozel, Julia E. Richards, Sayoko E. Moroi, Jonathan L. Haines, Jae H. Kang, Louis R. Pasquale, R. Rand Allingham, Allison Ashley-Koch, Paul Mitchell, Jie Jin Wang, Alan F. Wright, Craig Pennell, Timothy D. Spector, Terri L. Young, Caroline C.W. Klaver, Nicholas G. Martin, Grant W. Montgomery, Michael G. Anderson, Tin Aung, Colin E. Willoughby, Janey L. Wiggs, Chi P. Pang, Unnur Thorsteinsdottir, Andrew J. Lotery, Christopher J. Hammond, Cornelia M. Van Duijn, Michael A. Hauser, Yaron S. Rabinowitz, Norbert Pfeiffer, David A. MacKey, Jamie E. Craig, Stuart MacGregor^*, Tien Y. Wong

^*Corresponding author for this work

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

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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
DOIs	https://doi.org/10.1038/ng.2506
Publication status	Published - Feb 1 2013
Externally published	Yes

ASJC Scopus Subject Areas

Genetics

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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., ... Wong, T. Y. (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{d4e6081a39c8445abb69002737069c2a,

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 = "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 Tay, {Wan Ting} and Tai, {E. Shyong} and Cheng, {Ching Yu} and Jianjun Liu and Foo, {Jia Nee} 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 Xiaohui Li and David Siscovick and Taylor, {Kent D.} and Rotter, {Jerome I.} and Seyhan Yazar and Megan Ulmer and Jun Li and Yaspan, {Brian L.} and Ozel, {Ayse B.} and Richards, {Julia E.} and Moroi, {Sayoko E.} and Haines, {Jonathan L.} and Kang, {Jae H.} and Pasquale, {Louis R.} and Allingham, {R. Rand} and Allison Ashley-Koch and Paul Mitchell and Wang, {Jie Jin} and Wright, {Alan F.} and Craig Pennell and Spector, {Timothy D.} and Young, {Terri L.} and Klaver, {Caroline C.W.} and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Anderson, {Michael G.} and Tin Aung and Willoughby, {Colin E.} and Wiggs, {Janey L.} and Pang, {Chi P.} and Unnur Thorsteinsdottir and Lotery, {Andrew J.} and Hammond, {Christopher J.} and {Van Duijn}, {Cornelia M.} and Hauser, {Michael A.} and Rabinowitz, {Yaron S.} and Norbert Pfeiffer and MacKey, {David A.} and Craig, {Jamie E.} and Stuart MacGregor and Wong, {Tien Y.}",

year = "2013",

month = feb,

day = "1",

doi = "10.1038/ng.2506",

language = "English",

volume = "45",

pages = "155--163",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

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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, WT, Tai, ES, Cheng, CY, Liu, J, Foo, JN, 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, Li, X, Siscovick, D, Taylor, KD, Rotter, JI, Yazar, S, Ulmer, M, Li, J, Yaspan, BL, Ozel, AB, Richards, JE, Moroi, SE, Haines, JL, Kang, JH, Pasquale, LR, Allingham, RR, Ashley-Koch, A, Mitchell, P, Wang, JJ, Wright, AF, Pennell, C, Spector, TD, Young, TL, Klaver, CCW, Martin, NG, Montgomery, GW, Anderson, MG, Aung, T, Willoughby, CE, Wiggs, JL, Pang, CP, Thorsteinsdottir, U, Lotery, AJ, Hammond, CJ, Van Duijn, CM, Hauser, MA, Rabinowitz, YS, Pfeiffer, N, MacKey, DA, Craig, JE, MacGregor, S & Wong, TY 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 - 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 - Li, Xiaohui

AU - Siscovick, David

AU - Taylor, Kent D.

AU - Rotter, Jerome I.

AU - Yazar, Seyhan

AU - Ulmer, Megan

AU - Li, Jun

AU - Yaspan, Brian L.

AU - Ozel, Ayse B.

AU - Richards, Julia E.

AU - Moroi, Sayoko E.

AU - Haines, Jonathan L.

AU - Kang, Jae H.

AU - Pasquale, Louis R.

AU - Allingham, R. Rand

AU - Ashley-Koch, Allison

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Wright, Alan F.

AU - Pennell, Craig

AU - Spector, Timothy D.

AU - Young, Terri L.

AU - Klaver, Caroline C.W.

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Anderson, Michael G.

AU - Aung, Tin

AU - Willoughby, Colin E.

AU - Wiggs, Janey L.

AU - Pang, Chi P.

AU - Thorsteinsdottir, Unnur

AU - Lotery, Andrew J.

AU - Hammond, Christopher J.

AU - Van Duijn, Cornelia M.

AU - Hauser, Michael A.

AU - Rabinowitz, Yaron S.

AU - Pfeiffer, Norbert

AU - MacKey, David A.

AU - Craig, Jamie E.

AU - MacGregor, Stuart

AU - Wong, Tien Y.

PY - 2013/2/1

Y1 - 2013/2/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84947899509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947899509&partnerID=8YFLogxK

U2 - 10.1038/ng.2506

DO - 10.1038/ng.2506

M3 - Article

C2 - 23291589

AN - SCOPUS:84947899509

SN - 1061-4036

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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