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

CY (Ching-Yu) Cheng; M Schache; Kamran Ikram; TL Young; JA Guggenheim; V Vitart; S Macgregor; Virginie Verhoeven; VA Barathi; JM Liao; PG Hysi; JE Bailey-Wilson; B St Pourcain; JP Kemp; G McMahon; NJ Timpson; DM Evans; GW Montgomery; A Mishra; YX Wang; JJ Wang; E Rochtchina; O Polasek; AF Wright; Najaf Amin; Elisa Leeuwen; JF Wilson; CE Pennell; Cornelia Duijn; PTVM (Paulus) de Jong; Hans Vingerling; X Zhou; Peng Chen; RY Li; WT Tay; YF Zheng; M Chew; KP Burdon; JE Craig; SK Iyengar; RP Igo; JH Lass; EY Chew; T Haller; E Mihailov; A Metspalu; J Wedenoja; CL Simpson; R Wojciechowski; R Hohn; A Mirshahi; T Zeller; N Pfeiffer; KJ Lackner; T Bettecken; T Meitinger; K Oexle; M Pirastu; L Portas; A Nag; KM Williams; E Yonova-Doing; R Klein; BE Klein; SM Hosseini; AD Paterson; KM Makela; T Lehtimaki; M Kahonen; O Raitakari; N Yoshimura; F Matsuda; LJ Chen; CP Pang; SP Yip; MKH Yap; A Meguro; N Mizuki; H Inoko; PJ Foster; JH Zhao; E Vithana; ES Tai; Q Fan; L Xu; H Campbell; B Fleck; I Rudan; T Aung; Bert Hofman; André Uitterlinden; G Bencic; CC Khor; H Forward; O Parssinen; P Mitche; Fernando Rivadeneira; AW Hewitt; C Williams; Ben Oostra; YY Teo; CJ Hammond; D Stambolian; DA Mackey; Caroline Klaver; TY (Tien Yin) Wong; SM Saw; PN 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

CY (Ching-Yu) Cheng, M Schache, Kamran Ikram, TL Young, JA Guggenheim, V Vitart, S Macgregor, Virginie Verhoeven, VA Barathi, JM Liao, PG Hysi, JE Bailey-Wilson, B St Pourcain, JP Kemp, G McMahon, NJ Timpson, DM Evans, GW Montgomery, A Mishra, YX WangJJ Wang, E Rochtchina, O Polasek, AF Wright, Najaf Amin, Elisa Leeuwen, JF Wilson, CE Pennell, Cornelia Duijn, PTVM (Paulus) de Jong, Hans Vingerling, X Zhou, Peng Chen, RY Li, WT Tay, YF Zheng, M Chew, KP Burdon, JE Craig, SK Iyengar, RP Igo, JH Lass, EY Chew, T Haller, E Mihailov, A Metspalu, J Wedenoja, CL Simpson, R Wojciechowski, R Hohn, A Mirshahi, T Zeller, N Pfeiffer, KJ Lackner, T Bettecken, T Meitinger, K Oexle, M Pirastu, L Portas, A Nag, KM Williams, E Yonova-Doing, R Klein, BE Klein, SM Hosseini, AD Paterson, KM Makela, T Lehtimaki, M Kahonen, O Raitakari, N Yoshimura, F Matsuda, LJ Chen, CP Pang, SP Yip, MKH Yap, A Meguro, N Mizuki, H Inoko, PJ Foster, JH Zhao, E Vithana, ES Tai, Q Fan, L Xu, H Campbell, B Fleck, I Rudan, T Aung, Bert Hofman, André Uitterlinden, G Bencic, CC Khor, H Forward, O Parssinen, P Mitche, Fernando Rivadeneira, AW Hewitt, C Williams, Ben Oostra, YY Teo, CJ Hammond, D Stambolian, DA Mackey, Caroline Klaver, TY (Tien Yin) Wong, SM Saw, PN Baird

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

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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 - 2013

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EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC OR-01-60-01

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

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10.1016/j.ajhg.2013.06.016

http://hdl.handle.net/1765/55326

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Cheng, CY., Schache, M., Ikram, K., Young, TL., Guggenheim, JA., Vitart, V., Macgregor, S., Verhoeven, V., Barathi, VA., Liao, JM., Hysi, PG., Bailey-Wilson, JE., St Pourcain, B., Kemp, JP., McMahon, G., Timpson, NJ., Evans, DM., Montgomery, GW., Mishra, A., ... 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, 93(2), 264-277. https://doi.org/10.1016/j.ajhg.2013.06.016

@article{1289e5352c5a49a4b46cc9ff6a6f76b9,

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 = "Cheng, {CY (Ching-Yu)} and M Schache and Kamran Ikram and TL Young and JA Guggenheim and V Vitart and S Macgregor and Virginie Verhoeven and VA Barathi and JM Liao and PG Hysi and JE Bailey-Wilson and {St Pourcain}, B and JP Kemp and G McMahon and NJ Timpson and DM Evans and GW Montgomery and A Mishra and YX Wang and JJ Wang and E Rochtchina and O Polasek and AF Wright and Najaf Amin and Elisa Leeuwen and JF Wilson and CE Pennell and Cornelia Duijn and {de Jong}, {PTVM (Paulus)} and Hans Vingerling and X Zhou and Peng Chen and RY Li and WT Tay and YF Zheng and M Chew and KP Burdon and JE Craig and SK Iyengar and RP Igo and JH Lass and EY Chew and T Haller and E Mihailov and A Metspalu and J Wedenoja and CL Simpson and R Wojciechowski and R Hohn and A Mirshahi and T Zeller and N Pfeiffer and KJ Lackner and T Bettecken and T Meitinger and K Oexle and M Pirastu and L Portas and A Nag and KM Williams and E Yonova-Doing and R Klein and BE Klein and SM Hosseini and AD Paterson and KM Makela and T Lehtimaki and M Kahonen and O Raitakari and N Yoshimura and F Matsuda and LJ Chen and CP Pang and SP Yip and MKH Yap and A Meguro and N Mizuki and H Inoko and PJ Foster and JH Zhao and E Vithana and ES Tai and Q Fan and L Xu and H Campbell and B Fleck and I Rudan and T Aung and Bert Hofman and Andr{\'e} Uitterlinden and G Bencic and CC Khor and H Forward and O Parssinen and P Mitche and Fernando Rivadeneira and AW Hewitt and C Williams and Ben Oostra and YY Teo and CJ Hammond and D Stambolian and DA Mackey and Caroline Klaver and Wong, {TY (Tien Yin)} and SM Saw and PN Baird",

year = "2013",

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, CY, Schache, M, Ikram, K, Young, TL, Guggenheim, JA, Vitart, V, Macgregor, S, Verhoeven, V, Barathi, VA, Liao, JM, 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, Leeuwen, E, Wilson, JF, Pennell, CE, Duijn, C, de Jong, PTVM, Vingerling, H, Zhou, X, Chen, P, Li, RY, Tay, WT, Zheng, YF, 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, Hohn, R, Mirshahi, A, Zeller, T, Pfeiffer, N, Lackner, KJ, Bettecken, T, Meitinger, T, Oexle, K, Pirastu, M, Portas, L, Nag, A, Williams, KM, Yonova-Doing, E, Klein, R, Klein, BE, Hosseini, SM, Paterson, AD, Makela, KM, Lehtimaki, T, Kahonen, M, Raitakari, O, Yoshimura, N, Matsuda, F, Chen, LJ, Pang, CP, Yip, SP, Yap, MKH, Meguro, A, Mizuki, N, Inoko, H, Foster, PJ, Zhao, JH, Vithana, E, Tai, ES, Fan, Q, Xu, L, Campbell, H, Fleck, B, Rudan, I, Aung, T, Hofman, B , Uitterlinden, A, Bencic, G, Khor, CC, Forward, H, Parssinen, O, Mitche, P, Rivadeneira, F, Hewitt, AW, Williams, C, Oostra, B, Teo, YY, Hammond, CJ, Stambolian, D, Mackey, DA, Klaver, C, Wong, TY, Saw, SM & 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, CY (Ching-Yu)

AU - Schache, M

AU - Ikram, Kamran

AU - Young, TL

AU - Guggenheim, JA

AU - Vitart, V

AU - Macgregor, S

AU - Verhoeven, Virginie

AU - Barathi, VA

AU - Liao, JM

AU - Hysi, PG

AU - Bailey-Wilson, JE

AU - St Pourcain, B

AU - Kemp, JP

AU - McMahon, G

AU - Timpson, NJ

AU - Evans, DM

AU - Montgomery, GW

AU - Mishra, A

AU - Wang, YX

AU - Wang, JJ

AU - Rochtchina, E

AU - Polasek, O

AU - Wright, AF

AU - Amin, Najaf

AU - Leeuwen, Elisa

AU - Wilson, JF

AU - Pennell, CE

AU - Duijn, Cornelia

AU - de Jong, PTVM (Paulus)

AU - Vingerling, Hans

AU - Zhou, X

AU - Chen, Peng

AU - Li, RY

AU - Tay, WT

AU - Zheng, YF

AU - Chew, M

AU - Burdon, KP

AU - Craig, JE

AU - Iyengar, SK

AU - Igo, RP

AU - Lass, JH

AU - Chew, EY

AU - Haller, T

AU - Mihailov, E

AU - Metspalu, A

AU - Wedenoja, J

AU - Simpson, CL

AU - Wojciechowski, R

AU - Hohn, R

AU - Mirshahi, A

AU - Zeller, T

AU - Pfeiffer, N

AU - Lackner, KJ

AU - Bettecken, T

AU - Meitinger, T

AU - Oexle, K

AU - Pirastu, M

AU - Portas, L

AU - Nag, A

AU - Williams, KM

AU - Yonova-Doing, E

AU - Klein, R

AU - Klein, BE

AU - Hosseini, SM

AU - Paterson, AD

AU - Makela, KM

AU - Lehtimaki, T

AU - Kahonen, M

AU - Raitakari, O

AU - Yoshimura, N

AU - Matsuda, F

AU - Chen, LJ

AU - Pang, CP

AU - Yip, SP

AU - Yap, MKH

AU - Meguro, A

AU - Mizuki, N

AU - Inoko, H

AU - Foster, PJ

AU - Zhao, JH

AU - Vithana, E

AU - Tai, ES

AU - Fan, Q

AU - Xu, L

AU - Campbell, H

AU - Fleck, B

AU - Rudan, I

AU - Aung, T

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Bencic, G

AU - Khor, CC

AU - Forward, H

AU - Parssinen, O

AU - Mitche, P

AU - Rivadeneira, Fernando

AU - Hewitt, AW

AU - Williams, C

AU - Oostra, Ben

AU - Teo, YY

AU - Hammond, CJ

AU - Stambolian, D

AU - Mackey, DA

AU - Klaver, Caroline

AU - Wong, TY (Tien Yin)

AU - Saw, SM

AU - Baird, PN

PY - 2013

Y1 - 2013

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.

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

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