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, 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, Shea Ping Yip

Research output: Journal article publicationJournal articleAcademic researchpeer-review

128 Citations (Scopus)


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
Pages (from-to)264-277
Number of pages14
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished - 8 Aug 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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