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 & 88 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, Alireza Mirshahi, Tanja Zeller, Norbert Pfeiffer, Karl J. Lackner, Thomas Bettecken, Thomas Meitinger, Konrad Oexle, Mario Pirastu, Laura Portas, Abhishek Nag, Katie M. Williams, Ekaterina Yonova-Doing, Ronald Klein, Barbara E. Klein, S. Mohsen Hosseini, Andrew D. Paterson, Kari Matti Makela, Terho Lehtimaki, Mika Kahonen, Olli Raitakari, Nagahisa Yoshimura, Fumihiko Matsuda, Li Jia Chen, Chi Pui Pang, Shea Ping Yip, Maurice K H Yap, Akira Meguro, Nobuhisa Mizuki, Hidetoshi Inoko, Paul J. Foster, Jing Hua Zhao, Eranga Vithana, E. Shyong Tai, Qiao Fan, Liang Xu, Harry Campbell, Brian Fleck, Igor Rudan, Tin Aung, Albert Hofman, André G. Uitterlinden, Goran Bencic, Chiea Chuen Khor, Hannah Forward, Olavi Pärssinen, Paul Mitchell, Fernando Rivadeneira, Alex W. Hewitt, Cathy Williams, Ben A. Oostra, Yik Ying Teo, Christopher J. Hammond, Dwight Stambolian, David A. MacKey, Caroline C W Klaver, Tien Yin Wong, Seang Mei Saw, Paul N. Baird

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)264-277
Number of pages14
JournalAmerican Journal of Human Genetics
Volume93
Issue number2
DOIs
StatePublished - Aug 8 2013

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Eye Axial Length
Refractive Errors
Genome-Wide Association Study
Myopia
Hyperopia
Wnt Signaling Pathway
Lenses
Genes
Meta-Analysis
Public Health
Genome
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Makela, Kari Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E. Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik Ying; Hammond, Christopher J.; Stambolian, Dwight; MacKey, David A.; Klaver, Caroline C W; Wong, Tien Yin; Saw, Seang Mei; Baird, Paul N.

In: American Journal of Human Genetics, Vol. 93, No. 2, 08.08.2013, p. 264-277.

Research output: Contribution to journalArticle

Cheng, CY, 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, WT, 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, 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, A, Uitterlinden, AG, Bencic, G, Khor, CC, Forward, H, Pärssinen, O, Mitchell, P, Rivadeneira, F, Hewitt, AW, Williams, C, Oostra, BA, Teo, YY, Hammond, CJ, Stambolian, D, MacKey, DA, Klaver, CCW, 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
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 ; Mirshahi, Alireza ; Zeller, Tanja ; Pfeiffer, Norbert ; Lackner, Karl J. ; Bettecken, Thomas ; Meitinger, Thomas ; Oexle, Konrad ; Pirastu, Mario ; Portas, Laura ; Nag, Abhishek ; Williams, Katie M. ; Yonova-Doing, Ekaterina ; Klein, Ronald ; Klein, Barbara E. ; Hosseini, S. Mohsen ; Paterson, Andrew D. ; Makela, Kari Matti ; Lehtimaki, Terho ; Kahonen, Mika ; Raitakari, Olli ; Yoshimura, Nagahisa ; Matsuda, Fumihiko ; Chen, Li Jia ; Pang, Chi Pui ; Yip, Shea Ping ; Yap, Maurice K H ; Meguro, Akira ; Mizuki, Nobuhisa ; Inoko, Hidetoshi ; Foster, Paul J. ; Zhao, Jing Hua ; Vithana, Eranga ; Tai, E. Shyong ; Fan, Qiao ; Xu, Liang ; Campbell, Harry ; Fleck, Brian ; Rudan, Igor ; Aung, Tin ; Hofman, Albert ; Uitterlinden, André G. ; Bencic, Goran ; Khor, Chiea Chuen ; Forward, Hannah ; Pärssinen, Olavi ; Mitchell, Paul ; Rivadeneira, Fernando ; Hewitt, Alex W. ; Williams, Cathy ; Oostra, Ben A. ; Teo, Yik Ying ; Hammond, Christopher J. ; Stambolian, Dwight ; MacKey, David A. ; Klaver, Caroline C W ; Wong, Tien Yin ; Saw, Seang Mei ; Baird, Paul N. / 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. 264-277.
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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.",
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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 - Mirshahi, Alireza

AU - Zeller, Tanja

AU - Pfeiffer, Norbert

AU - Lackner, Karl J.

AU - Bettecken, Thomas

AU - Meitinger, Thomas

AU - Oexle, Konrad

AU - Pirastu, Mario

AU - Portas, Laura

AU - Nag, Abhishek

AU - Williams, Katie M.

AU - Yonova-Doing, Ekaterina

AU - Klein, Ronald

AU - Klein, Barbara E.

AU - Hosseini, S. Mohsen

AU - Paterson, Andrew D.

AU - Makela, Kari Matti

AU - Lehtimaki, Terho

AU - Kahonen, Mika

AU - Raitakari, Olli

AU - Yoshimura, Nagahisa

AU - Matsuda, Fumihiko

AU - Chen, Li Jia

AU - Pang, Chi Pui

AU - Yip, Shea Ping

AU - Yap, Maurice K H

AU - Meguro, Akira

AU - Mizuki, Nobuhisa

AU - Inoko, Hidetoshi

AU - Foster, Paul J.

AU - Zhao, Jing Hua

AU - Vithana, Eranga

AU - Tai, E. Shyong

AU - Fan, Qiao

AU - Xu, Liang

AU - Campbell, Harry

AU - Fleck, Brian

AU - Rudan, Igor

AU - Aung, Tin

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Bencic, Goran

AU - Khor, Chiea Chuen

AU - Forward, Hannah

AU - Pärssinen, Olavi

AU - Mitchell, Paul

AU - Rivadeneira, Fernando

AU - Hewitt, Alex W.

AU - Williams, Cathy

AU - Oostra, Ben A.

AU - Teo, Yik Ying

AU - Hammond, Christopher J.

AU - Stambolian, Dwight

AU - MacKey, David A.

AU - Klaver, Caroline C W

AU - Wong, Tien Yin

AU - Saw, Seang Mei

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.

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U2 - 10.1016/j.ajhg.2013.06.016

DO - 10.1016/j.ajhg.2013.06.016

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EP - 277

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

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