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 & 31 others 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, Juho Wedenoja, Claire L Simpson, Robert Wojciechowski, René Höhn, Consortium for Refractive Error and Myopia

Research output: Contribution to journalArticle

70 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.

LanguageEnglish
Pages264-77
Number of pages14
JournalAmerican Journal of Human Genetics
Volume93
Issue number2
DOIs
Publication statusPublished - 8 Aug 2013
Externally publishedYes

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
  • Journal Article
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

Cite this

Cheng, C-Y., Schache, M., Ikram, M. K., Young, T. L., Guggenheim, J. A., Vitart, V., ... Consortium for Refractive Error and Myopia (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), 264-77. https://doi.org/10.1016/j.ajhg.2013.06.016
Cheng, Ching-Yu ; Schache, Maria ; Ikram, M Kamran ; Young, Terri L ; Guggenheim, Jeremy A ; Vitart, Veronique ; MacGregor, Stuart ; Verhoeven, Virginie J M ; Barathi, Veluchamy A ; Liao, Jiemin ; Hysi, Pirro G ; Bailey-Wilson, Joan E ; St Pourcain, Beate ; Kemp, John P ; McMahon, George ; Timpson, Nicholas J ; Evans, David M ; Montgomery, Grant W ; Mishra, Aniket ; Wang, Ya Xing ; Wang, Jie Jin ; Rochtchina, Elena ; Polasek, Ozren ; Wright, Alan F ; Amin, Najaf ; van Leeuwen, Elisabeth M ; Wilson, James F ; Pennell, Craig E ; van Duijn, Cornelia M ; de Jong, Paulus T V M ; Vingerling, Johannes R ; Zhou, Xin ; Chen, Peng ; Li, Ruoying ; Tay, Wan-Ting ; Zheng, Yingfeng ; Chew, Merwyn ; Burdon, Kathryn P ; Craig, Jamie E ; Iyengar, Sudha K ; Igo, Robert P ; Lass, Jonathan H ; Chew, Emily Y ; Haller, Toomas ; Mihailov, Evelin ; Metspalu, Andres ; Wedenoja, Juho ; Simpson, Claire L ; Wojciechowski, Robert ; Höhn, René ; Consortium for Refractive Error and Myopia. / Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. In: American Journal of Human Genetics. 2013 ; Vol. 93, No. 2. pp. 264-77.
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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.",
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, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't",
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 Juho Wedenoja and Simpson, {Claire L} and Robert Wojciechowski and Ren{\'e} H{\"o}hn and {Consortium for Refractive Error and Myopia}",
note = "Copyright {\circledC} 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = "8",
day = "8",
doi = "10.1016/j.ajhg.2013.06.016",
language = "English",
volume = "93",
pages = "264--77",
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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, Wedenoja, J, Simpson, CL, Wojciechowski, R, Höhn, R & Consortium for Refractive Error and Myopia 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. 264-77. https://doi.org/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. / Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Consortium for Refractive Error and Myopia.

In: American Journal of Human Genetics, Vol. 93, No. 2, 08.08.2013, p. 264-77.

Research output: Contribution to journalArticle

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 - Wedenoja, Juho

AU - Simpson, Claire L

AU - Wojciechowski, Robert

AU - Höhn, René

AU - Consortium for Refractive Error and Myopia

N1 - Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ajhg.2013.06.016

DO - 10.1016/j.ajhg.2013.06.016

M3 - Article

VL - 93

SP - 264

EP - 277

JO - American Journal of Human Genetics

T2 - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -