Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

Chingyu Cheng; Maria Schache; Mohammad Ikram; Terri Young; J Guggenheim; Véronique Vitart; Stuart Macgregor; V Verhoeven; Veluchamy Barathi; Jiemin Liao; Pirro Hysi; Joan Bailey-Wilson; Beate St. Pourcain; John Kemp; George McMahon; Nicholas Timpson; David Evans; Grant Montgomery; Aniket Mishra; Yaxing Wang; Jiejin Wang; E Rochtchina; Ozren Polasek; Alan Wright; Najaf Amin; Elisabeth Van Leeuwen; James Wilson; Craig Pennell; Cornelia van Duijn; Paulus De Jong; Johannes Vingerling; Xin Zhou; Peng Chen; Ruoying Li; Wanting Tay; Yingfeng Zheng; Merwyn Chew; Kathryn Burdon; Jamie Craig; Sudha Iyengar; Robert Igo; Jonathan Lass; Emily Chew; Toomas Haller; Evelin Mihailov; Andres Metspalu; Juho Wedenoja; Claire Simpson; Robert Wojciechowski; Rene Hohn; Alireza Mirshahi; Tanja Zeller; Norbert Pfeiffer; Karl Lackner; Thomas Bettecken; Thomas Meitinger; Konrad Oexle; Mario Pirastu; Laura Portas; Abhishek Nag; Katie Williams; Ekaterina Yonova-Doing; Ronald Klein; Barbara Klein; S Hosseini; Andrew Paterson; Kari Makela; Terho Lehtimaki; Mika Kahonen; Olli Raitakari; Nagahisa Yoshimura; Fumihiko Matsuda; Lijia Chen; Chipui Pang; Sheaping Yip; Maurice Yap; Akira Meguro; Nobuhisa Mizuki; Hidetoshi Inoko; Paul Foster; Jinghua Zhao; Eranga Vithana; E Tai; Qiao Fan; Liang Xu; Harry Campbell; Brian Fleck; Igor Rudan; Tin Aung; Albert Hofman; André Uitterlinden; Goran Bencic; Chiea Khor; Hannah Forward; Olavi Parssinen; Paul Mitchell; Fernando Rivadeneira; Alex Hewitt; Cathy Williams; Ben Oostra; Yikying Teo; Christopher Hammond; Dwight Stambolian; David Mackey; Caroline Klaver; Tienyin Wong; Seangmei Saw; Paul N. Baird

doi:10.1016/j.ajhg.2013.06.016

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

Chingyu Cheng, Maria Schache, Mohammad Ikram, Terri Young, J Guggenheim, Véronique Vitart, Stuart Macgregor, V Verhoeven, Veluchamy Barathi, Jiemin Liao, Pirro Hysi, Joan Bailey-Wilson, Beate St. Pourcain, John Kemp, George McMahon, Nicholas Timpson, David Evans, Grant Montgomery, Aniket Mishra, Yaxing WangJiejin Wang, E Rochtchina, Ozren Polasek, Alan Wright, Najaf Amin, Elisabeth Van Leeuwen, James Wilson, Craig Pennell, Cornelia van Duijn, Paulus De Jong, Johannes Vingerling, Xin Zhou, Peng Chen, Ruoying Li, Wanting Tay, Yingfeng Zheng, Merwyn Chew, Kathryn Burdon, Jamie Craig, Sudha Iyengar, Robert Igo, Jonathan Lass, Emily Chew, Toomas Haller, Evelin Mihailov, Andres Metspalu, Juho Wedenoja, Claire Simpson, Robert Wojciechowski, Rene Hohn, Alireza Mirshahi, Tanja Zeller, Norbert Pfeiffer, Karl Lackner, Thomas Bettecken, Thomas Meitinger, Konrad Oexle, Mario Pirastu, Laura Portas, Abhishek Nag, Katie Williams, Ekaterina Yonova-Doing, Ronald Klein, Barbara Klein, S Hosseini, Andrew Paterson, Kari Makela, Terho Lehtimaki, Mika Kahonen, Olli Raitakari, Nagahisa Yoshimura, Fumihiko Matsuda, Lijia Chen, Chipui Pang, Sheaping Yip, Maurice Yap, Akira Meguro, Nobuhisa Mizuki, Hidetoshi Inoko, Paul Foster, Jinghua Zhao, Eranga Vithana, E Tai, Qiao Fan, Liang Xu, Harry Campbell, Brian Fleck, Igor Rudan, Tin Aung, Albert Hofman, André Uitterlinden, Goran Bencic, Chiea Khor, Hannah Forward, Olavi Parssinen, Paul Mitchell, Fernando Rivadeneira, Alex Hewitt, Cathy Williams, Ben Oostra, Yikying Teo, Christopher Hammond, Dwight Stambolian, David Mackey, Caroline Klaver, Tienyin Wong, Seangmei Saw, Paul N. Baird

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Abstract

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

Original language	English
Pages (from-to)	264-277
Number of pages	14
Journal	American Journal of Human Genetics
Volume	93
Issue number	2
DOIs	https://doi.org/10.1016/j.ajhg.2013.06.016
Publication status	Published - 8 Aug 2013

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Cheng, C., Schache, M., Ikram, M., Young, T., Guggenheim, J., Vitart, V., Macgregor, S., Verhoeven, V., Barathi, V., Liao, J., Hysi, P., Bailey-Wilson, J., St. Pourcain, B., Kemp, J., McMahon, G., Timpson, N., Evans, D., Montgomery, G., Mishra, A., ... Baird, P. N. (2013). Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. American Journal of Human Genetics, 93(2), 264-277. https://doi.org/10.1016/j.ajhg.2013.06.016

@article{1d2278bedfe34dd7a62faf34d79f47bf,

title = "Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error",

abstract = "Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.",

author = "Chingyu Cheng and Maria Schache and Mohammad Ikram and Terri Young and J Guggenheim and V{\'e}ronique Vitart and Stuart Macgregor and V Verhoeven and Veluchamy Barathi and Jiemin Liao and Pirro Hysi and Joan Bailey-Wilson and {St. Pourcain}, Beate and John Kemp and George McMahon and Nicholas Timpson and David Evans and Grant Montgomery and Aniket Mishra and Yaxing Wang and Jiejin Wang and E Rochtchina and Ozren Polasek and Alan Wright and Najaf Amin and {Van Leeuwen}, Elisabeth and James Wilson and Craig Pennell and {van Duijn}, Cornelia and {De Jong}, Paulus and Johannes Vingerling and Xin Zhou and Peng Chen and Ruoying Li and Wanting Tay and Yingfeng Zheng and Merwyn Chew and Kathryn Burdon and Jamie Craig and Sudha Iyengar and Robert Igo and Jonathan Lass and Emily Chew and Toomas Haller and Evelin Mihailov and Andres Metspalu and Juho Wedenoja and Claire Simpson and Robert Wojciechowski and Rene Hohn and Alireza Mirshahi and Tanja Zeller and Norbert Pfeiffer and Karl Lackner and Thomas Bettecken and Thomas Meitinger and Konrad Oexle and Mario Pirastu and Laura Portas and Abhishek Nag and Katie Williams and Ekaterina Yonova-Doing and Ronald Klein and Barbara Klein and S Hosseini and Andrew Paterson and Kari Makela and Terho Lehtimaki and Mika Kahonen and Olli Raitakari and Nagahisa Yoshimura and Fumihiko Matsuda and Lijia Chen and Chipui Pang and Sheaping Yip and Maurice Yap and Akira Meguro and Nobuhisa Mizuki and Hidetoshi Inoko and Paul Foster and Jinghua Zhao and Eranga Vithana and E Tai and Qiao Fan and Liang Xu and Harry Campbell and Brian Fleck and Igor Rudan and Tin Aung and Albert Hofman and Andr{\'e} Uitterlinden and Goran Bencic and Chiea Khor and Hannah Forward and Olavi Parssinen and Paul Mitchell and Fernando Rivadeneira and Alex Hewitt and Cathy Williams and Ben Oostra and Yikying Teo and Christopher Hammond and Dwight Stambolian and David Mackey and Caroline Klaver and Tienyin Wong and Seangmei Saw and Baird, {Paul N.}",

year = "2013",

month = aug,

day = "8",

doi = "10.1016/j.ajhg.2013.06.016",

language = "English",

volume = "93",

pages = "264--277",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "2",

}

Cheng, C, Schache, M, Ikram, M, Young, T, Guggenheim, J, Vitart, V, Macgregor, S, Verhoeven, V, Barathi, V, Liao, J, Hysi, P, Bailey-Wilson, J, St. Pourcain, B, Kemp, J, McMahon, G, Timpson, N, Evans, D, Montgomery, G, Mishra, A, Wang, Y, Wang, J, Rochtchina, E, Polasek, O, Wright, A, Amin, N, Van Leeuwen, E, Wilson, J, Pennell, C, van Duijn, C, De Jong, P, Vingerling, J, Zhou, X, Chen, P, Li, R, Tay, W, Zheng, Y, Chew, M, Burdon, K, Craig, J, Iyengar, S, Igo, R, Lass, J, Chew, E, Haller, T, Mihailov, E, Metspalu, A, Wedenoja, J, Simpson, C, Wojciechowski, R, Hohn, R, Mirshahi, A, Zeller, T, Pfeiffer, N, Lackner, K, Bettecken, T, Meitinger, T, Oexle, K, Pirastu, M, Portas, L, Nag, A, Williams, K, Yonova-Doing, E, Klein, R, Klein, B, Hosseini, S, Paterson, A, Makela, K, Lehtimaki, T, Kahonen, M, Raitakari, O, Yoshimura, N, Matsuda, F, Chen, L, Pang, C, Yip, S, Yap, M, Meguro, A, Mizuki, N, Inoko, H, Foster, P, Zhao, J, Vithana, E, Tai, E, Fan, Q, Xu, L, Campbell, H, Fleck, B, Rudan, I, Aung, T, Hofman, A, Uitterlinden, A, Bencic, G, Khor, C, Forward, H, Parssinen, O, Mitchell, P, Rivadeneira, F, Hewitt, A, Williams, C, Oostra, B, Teo, Y, Hammond, C, Stambolian, D, Mackey, D, Klaver, C, Wong, T, Saw, S & Baird, PN 2013, 'Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error', American Journal of Human Genetics, vol. 93, no. 2, pp. 264-277. https://doi.org/10.1016/j.ajhg.2013.06.016

TY - JOUR

T1 - Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

AU - Cheng, Chingyu

AU - Schache, Maria

AU - Ikram, Mohammad

AU - Young, Terri

AU - Guggenheim, J

AU - Vitart, Véronique

AU - Macgregor, Stuart

AU - Verhoeven, V

AU - Barathi, Veluchamy

AU - Liao, Jiemin

AU - Hysi, Pirro

AU - Bailey-Wilson, Joan

AU - St. Pourcain, Beate

AU - Kemp, John

AU - McMahon, George

AU - Timpson, Nicholas

AU - Evans, David

AU - Montgomery, Grant

AU - Mishra, Aniket

AU - Wang, Yaxing

AU - Wang, Jiejin

AU - Rochtchina, E

AU - Polasek, Ozren

AU - Wright, Alan

AU - Amin, Najaf

AU - Van Leeuwen, Elisabeth

AU - Wilson, James

AU - Pennell, Craig

AU - van Duijn, Cornelia

AU - De Jong, Paulus

AU - Vingerling, Johannes

AU - Zhou, Xin

AU - Chen, Peng

AU - Li, Ruoying

AU - Tay, Wanting

AU - Zheng, Yingfeng

AU - Chew, Merwyn

AU - Burdon, Kathryn

AU - Craig, Jamie

AU - Iyengar, Sudha

AU - Igo, Robert

AU - Lass, Jonathan

AU - Chew, Emily

AU - Haller, Toomas

AU - Mihailov, Evelin

AU - Metspalu, Andres

AU - Wedenoja, Juho

AU - Simpson, Claire

AU - Wojciechowski, Robert

AU - Hohn, Rene

AU - Mirshahi, Alireza

AU - Zeller, Tanja

AU - Pfeiffer, Norbert

AU - Lackner, Karl

AU - Bettecken, Thomas

AU - Meitinger, Thomas

AU - Oexle, Konrad

AU - Pirastu, Mario

AU - Portas, Laura

AU - Nag, Abhishek

AU - Williams, Katie

AU - Yonova-Doing, Ekaterina

AU - Klein, Ronald

AU - Klein, Barbara

AU - Hosseini, S

AU - Paterson, Andrew

AU - Makela, Kari

AU - Lehtimaki, Terho

AU - Kahonen, Mika

AU - Raitakari, Olli

AU - Yoshimura, Nagahisa

AU - Matsuda, Fumihiko

AU - Chen, Lijia

AU - Pang, Chipui

AU - Yip, Sheaping

AU - Yap, Maurice

AU - Meguro, Akira

AU - Mizuki, Nobuhisa

AU - Inoko, Hidetoshi

AU - Foster, Paul

AU - Zhao, Jinghua

AU - Vithana, Eranga

AU - Tai, E

AU - Fan, Qiao

AU - Xu, Liang

AU - Campbell, Harry

AU - Fleck, Brian

AU - Rudan, Igor

AU - Aung, Tin

AU - Hofman, Albert

AU - Uitterlinden, André

AU - Bencic, Goran

AU - Khor, Chiea

AU - Forward, Hannah

AU - Parssinen, Olavi

AU - Mitchell, Paul

AU - Rivadeneira, Fernando

AU - Hewitt, Alex

AU - Williams, Cathy

AU - Oostra, Ben

AU - Teo, Yikying

AU - Hammond, Christopher

AU - Stambolian, Dwight

AU - Mackey, David

AU - Klaver, Caroline

AU - Wong, Tienyin

AU - Saw, Seangmei

AU - Baird, Paul N.

PY - 2013/8/8

Y1 - 2013/8/8

N2 - Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

AB - Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

UR - http://www.scopus.com/inward/record.url?scp=84881647995&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2013.06.016

DO - 10.1016/j.ajhg.2013.06.016

M3 - Article

SN - 0002-9297

VL - 93

SP - 264

EP - 277

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 2

ER -

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

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