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 Thorleifsson; Kari 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

doi:10.1038/ng.2506

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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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 - 1 Feb 2013

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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

@article{a1f4a5d03e3a4de49b4deef1e8a53c31,

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 Kathryn Burdon and Chiea-Chuen Khor and Yelena Bykhovskaya and Alireza Mirshahi and Alex Hewitt and Demelza Koehn and Pirro Hysi and Wishal Ramdas and Tanja Zeller and Eranga Vithana and Belinda Cornes and Wan-Ting Tay and E-Shyong Tai and Ching-Yu Cheng and Jianjun Liu and Jia-Nee Foo and Seang-Mei Saw and Gudmar Thorleifsson and Kari Stefansson and David Dimasi and Richard Mills and Jenny Mountain and Wei Ang and Ren{\'e} Hoehn and Virginie Verhoeven and Franz Grus and Roger Wolfs and Rapha{\"e}le Castagne and Karl Lackner and Hanri{\"e}t Springelkamp and Jian Yang and Fridbert Jonasson and Dexter Leung and Li Chen and Clement Tham and Igor Rudan and Zoran Vatavuk and Caroline Hayward and Jane Gibson and Angela Cree and Alex Macleod and Sarah Ennis and Ozren Polasek and Harry Campbell and James Wilson and Ananth Viswanathan and Brian Fleck and Xiaohui Li and David Siscovick and Kent Taylor and Jerome Rotter and Seyhan Yazar and Megan Ulmer and Jun Li and Brian Yaspan and Ayse Ozel and Julia Richards and Sayoko Moroi and Jonathan Haines and Jae Kang and Louis Pasquale and R Allingham and Allison Ashely-Koch and Paul Mitchell and Wang, {Jie Jin} and Alan Wright and Craig Pennell and Timothy Spector and Terri Young and Caroline Klaver and Nicholas Martin and Grant Montgomery and Michael Anderson and Tin Aung and Colin Willoughby and Janey Wiggs and Pang, {Chi Pui} and Unnur Thorsteinsdottir and Andrew Lotery and Christopher Hammond and {van Duijn}, Cornelia and Michael Hauser and Yaron Rabinowitz and Norbert Pfeiffer and David Mackey and Jamie Craig and Stuart Macgregor and Tien Wong",

year = "2013",

month = feb,

day = "1",

doi = "10.1038/ng.2506",

language = "English",

volume = "45",

pages = "155--163",

journal = "Nature Genetics",

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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, Thorleifsson, G, Stefansson, K, Dimasi, D, Mills, R, Mountain, J, Ang, W, Hoehn, R, Verhoeven, V, Grus, F, Wolfs, R, Castagne, R, Lackner, K, Springelkamp, H, Yang, J, Jonasson, F, Leung, D, Chen, L, Tham, C, Rudan, I, Vatavuk, Z, Hayward, C, Gibson, J, Cree, A, Macleod, A, Ennis, S, Polasek, O, Campbell, H, Wilson, J, Viswanathan, A, Fleck, B, Li, X, Siscovick, D, Taylor, K, Rotter, J, Yazar, S, Ulmer, M, Li, J, Yaspan, B, Ozel, A, Richards, J, Moroi, S, Haines, J, Kang, J, Pasquale, L, Allingham, R, Ashely-Koch, A, Mitchell, P, Wang, JJ, Wright, A, Pennell, C, Spector, T, Young, T, Klaver, C, Martin, N, Montgomery, G, Anderson, M, Aung, T, Willoughby, C, Wiggs, J, Pang, CP, Thorsteinsdottir, U, Lotery, A, Hammond, C, van Duijn, C, Hauser, M, Rabinowitz, Y, Pfeiffer, N, Mackey, D, Craig, J, Macgregor, S & Wong, T 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

AU - Khor, Chiea-Chuen

AU - Bykhovskaya, Yelena

AU - Mirshahi, Alireza

AU - Hewitt, Alex

AU - Koehn, Demelza

AU - Hysi, Pirro

AU - Ramdas, Wishal

AU - Zeller, Tanja

AU - Vithana, Eranga

AU - Cornes, Belinda

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

AU - Mills, Richard

AU - Mountain, Jenny

AU - Ang, Wei

AU - Hoehn, René

AU - Verhoeven, Virginie

AU - Grus, Franz

AU - Wolfs, Roger

AU - Castagne, Raphaële

AU - Lackner, Karl

AU - Springelkamp, Hanriët

AU - Yang, Jian

AU - Jonasson, Fridbert

AU - Leung, Dexter

AU - Chen, Li

AU - Tham, Clement

AU - Rudan, Igor

AU - Vatavuk, Zoran

AU - Hayward, Caroline

AU - Gibson, Jane

AU - Cree, Angela

AU - Macleod, Alex

AU - Ennis, Sarah

AU - Polasek, Ozren

AU - Campbell, Harry

AU - Wilson, James

AU - Viswanathan, Ananth

AU - Fleck, Brian

AU - Li, Xiaohui

AU - Siscovick, David

AU - Taylor, Kent

AU - Rotter, Jerome

AU - Yazar, Seyhan

AU - Ulmer, Megan

AU - Li, Jun

AU - Yaspan, Brian

AU - Ozel, Ayse

AU - Richards, Julia

AU - Moroi, Sayoko

AU - Haines, Jonathan

AU - Kang, Jae

AU - Pasquale, Louis

AU - Allingham, R

AU - Ashely-Koch, Allison

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Wright, Alan

AU - Pennell, Craig

AU - Spector, Timothy

AU - Young, Terri

AU - Klaver, Caroline

AU - Martin, Nicholas

AU - Montgomery, Grant

AU - Anderson, Michael

AU - Aung, Tin

AU - Willoughby, Colin

AU - Wiggs, Janey

AU - Pang, Chi Pui

AU - Thorsteinsdottir, Unnur

AU - Lotery, Andrew

AU - Hammond, Christopher

AU - van Duijn, Cornelia

AU - Hauser, Michael

AU - Rabinowitz, Yaron

AU - Pfeiffer, Norbert

AU - Mackey, David

AU - Craig, Jamie

AU - Macgregor, Stuart

AU - Wong, Tien

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

U2 - 10.1038/ng.2506

DO - 10.1038/ng.2506

M3 - Article

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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