Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

Ching-Yu Cheng; Maria Schache; M. Kamran Ikram; Terri L. Young; Jeremy A. Guggenheim; Veronique Vitart; Stuart MacGregor; Virginie J. M. Verhoeven; Veluchamy A. Barathi; Jiemin Liao; Pirro G. Hysi; Joan E. Bailey-Wilson; Beate St Pourcain; John P. Kemp; George McMahon; Nicholas J. Timpson; David M. Evans; Grant W. Montgomery; Aniket Mishra; Ya Xing Wang; Jie Jin Wang; Elena Rochtchina; Ozren Polasek; Alan F. Wright; Najaf Amin; Elisabeth M. van Leeuwen; James F. Wilson; Craig E. Pennell; Cornelia M. van Duijn; Paulus T. V. M. de Jong; Johannes R. Vingerling; Xin Zhou; Peng Chen; Ruoying Li; Wan-Ting Tay; Yingfeng Zheng; Merwyn Chew; Kathryn P. Burdon; Jamie E. Craig; Sudha K. Iyengar; Robert P. Igo; Jonathan H. Lass; Emily Y. Chew; Toomas Haller; Evelin Mihailov; Andres Metspalu; Abhishek Nag; Katherine Williams; Christopher J. Hammond; Consortium Refractive Error Myopia; Fuchs Genetics Multictr Study Grp; Wellcome Trust Case Control Consor; Diabet Control Complications Trial

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

Ching-Yu Cheng, Maria Schache, M. Kamran Ikram, Terri L. Young, Jeremy A. Guggenheim, Veronique Vitart, Stuart MacGregor, Virginie J. M. Verhoeven, Veluchamy A. Barathi, Jiemin Liao, Pirro G. Hysi, Joan E. Bailey-Wilson, Beate St Pourcain, John P. Kemp, George McMahon, Nicholas J. Timpson, David M. Evans, Grant W. Montgomery, Aniket Mishra, Ya Xing WangJie Jin Wang, Elena Rochtchina, Ozren Polasek, Alan F. Wright, Najaf Amin, Elisabeth M. van Leeuwen, James F. Wilson, Craig E. Pennell, Cornelia M. van Duijn, Paulus T. V. M. de Jong, Johannes R. Vingerling, Xin Zhou, Peng Chen, Ruoying Li, Wan-Ting Tay, Yingfeng Zheng, Merwyn Chew, Kathryn P. Burdon, Jamie E. Craig, Sudha K. Iyengar, Robert P. Igo, Jonathan H. Lass, Emily Y. Chew, Toomas Haller, Evelin Mihailov, Andres Metspalu, Abhishek Nag, Katherine Williams, Christopher J. Hammond, Consortium Refractive Error Myopia, Fuchs Genetics Multictr Study Grp, Wellcome Trust Case Control Consor, Diabet Control Complications Trial

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133 Citations (Scopus)

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

Keywords

Adolescent
Adult
Aged
Asian Continental Ancestry Group
Axial Length, Eye
European Continental Ancestry Group
Eye Proteins
Female
Gene Expression
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Refractive Errors
Signal Transduction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ajhg.2013.06.016

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Cheng, C.-Y., Schache, M., Ikram, M. K., Young, T. L., Guggenheim, J. A., Vitart, V., MacGregor, S., Verhoeven, V. J. M., Barathi, V. A., Liao, J., Hysi, P. G., Bailey-Wilson, J. E., St Pourcain, B., Kemp, J. P., McMahon, G., Timpson, N. J., Evans, D. M., Montgomery, G. W., Mishra, A., ... Diabet Control Complications Trial (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{5129c0439f294634bdab291c7f91eb22,

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.",

keywords = "Adolescent, Adult, Aged, Asian Continental Ancestry Group, Axial Length, Eye, European Continental Ancestry Group, Eye Proteins, Female, Gene Expression, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Refractive Errors, Signal Transduction",

author = "Ching-Yu Cheng and Maria Schache and Ikram, {M. Kamran} and Young, {Terri L.} and Guggenheim, {Jeremy A.} and Veronique Vitart and Stuart MacGregor and Verhoeven, {Virginie J. M.} and Barathi, {Veluchamy A.} and Jiemin Liao and Hysi, {Pirro G.} and Bailey-Wilson, {Joan E.} and {St Pourcain}, Beate and Kemp, {John P.} and George McMahon and Timpson, {Nicholas J.} and Evans, {David M.} and Montgomery, {Grant W.} and Aniket Mishra and Wang, {Ya Xing} and Wang, {Jie Jin} and Elena Rochtchina and Ozren Polasek and Wright, {Alan F.} and Najaf Amin and {van Leeuwen}, {Elisabeth M.} and Wilson, {James F.} and Pennell, {Craig E.} and {van Duijn}, {Cornelia M.} and {de Jong}, {Paulus T. V. M.} and Vingerling, {Johannes R.} and Xin Zhou and Peng Chen and Ruoying Li and Wan-Ting Tay and Yingfeng Zheng and Merwyn Chew and Burdon, {Kathryn P.} and Craig, {Jamie E.} and Iyengar, {Sudha K.} and Igo, {Robert P.} and Lass, {Jonathan H.} and Chew, {Emily Y.} and Toomas Haller and Evelin Mihailov and Andres Metspalu and Abhishek Nag and Katherine Williams and Hammond, {Christopher J.} and {Consortium Refractive Error Myopia} and {Fuchs Genetics Multictr Study Grp} and {Wellcome Trust Case Control Consor} and {Diabet Control Complications Trial} and Robert Plomin",

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 = "Elsevier",

number = "2",

}

Cheng, C-Y, Schache, M, Ikram, MK, Young, TL, Guggenheim, JA, Vitart, V, MacGregor, S, Verhoeven, VJM, Barathi, VA, Liao, J, Hysi, PG, Bailey-Wilson, JE, St Pourcain, B, Kemp, JP, McMahon, G, Timpson, NJ, Evans, DM, Montgomery, GW, Mishra, A, Wang, YX, Wang, JJ, Rochtchina, E, Polasek, O, Wright, AF, Amin, N, van Leeuwen, EM, Wilson, JF, Pennell, CE, van Duijn, CM, de Jong, PTVM, Vingerling, JR, Zhou, X, Chen, P, Li, R, Tay, W-T, Zheng, Y, Chew, M, Burdon, KP, Craig, JE, Iyengar, SK, Igo, RP, Lass, JH, Chew, EY, Haller, T, Mihailov, E, Metspalu, A, Nag, A , Williams, K , Hammond, CJ, Consortium Refractive Error Myopia, Fuchs Genetics Multictr Study Grp, Wellcome Trust Case Control Consor & Diabet Control Complications Trial 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, Ching-Yu

AU - Schache, Maria

AU - Ikram, M. Kamran

AU - Young, Terri L.

AU - Guggenheim, Jeremy A.

AU - Vitart, Veronique

AU - MacGregor, Stuart

AU - Verhoeven, Virginie J. M.

AU - Barathi, Veluchamy A.

AU - Liao, Jiemin

AU - Hysi, Pirro G.

AU - Bailey-Wilson, Joan E.

AU - St Pourcain, Beate

AU - Kemp, John P.

AU - McMahon, George

AU - Timpson, Nicholas J.

AU - Evans, David M.

AU - Montgomery, Grant W.

AU - Mishra, Aniket

AU - Wang, Ya Xing

AU - Wang, Jie Jin

AU - Rochtchina, Elena

AU - Polasek, Ozren

AU - Wright, Alan F.

AU - Amin, Najaf

AU - van Leeuwen, Elisabeth M.

AU - Wilson, James F.

AU - Pennell, Craig E.

AU - van Duijn, Cornelia M.

AU - de Jong, Paulus T. V. M.

AU - Vingerling, Johannes R.

AU - Zhou, Xin

AU - Chen, Peng

AU - Li, Ruoying

AU - Tay, Wan-Ting

AU - Zheng, Yingfeng

AU - Chew, Merwyn

AU - Burdon, Kathryn P.

AU - Craig, Jamie E.

AU - Iyengar, Sudha K.

AU - Igo, Robert P.

AU - Lass, Jonathan H.

AU - Chew, Emily Y.

AU - Haller, Toomas

AU - Mihailov, Evelin

AU - Metspalu, Andres

AU - Nag, Abhishek

AU - Williams, Katherine

AU - Hammond, Christopher J.

AU - Consortium Refractive Error Myopia

AU - Fuchs Genetics Multictr Study Grp

AU - Wellcome Trust Case Control Consor

AU - Diabet Control Complications Trial

AU - Plomin, Robert

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Asian Continental Ancestry Group

KW - Axial Length, Eye

KW - European Continental Ancestry Group

KW - Eye Proteins

KW - Female

KW - Gene Expression

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Refractive Errors

KW - Signal Transduction

U2 - 10.1016/j.ajhg.2013.06.016

DO - 10.1016/j.ajhg.2013.06.016

M3 - Article

C2 - 24144296

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

Abstract

Keywords

UN SDGs

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