Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

Chingyu Cheng, Maria Schache, Mohammad Ikram, Terri Young, J Guggenheim, Véronique Vitart, Stuart Macgregor, V Verhoeven, Veluchamy Barathi, Jiemin Liao, Pirro Hysi, Joan Bailey-Wilson, Beate St. Pourcain, John Kemp, George McMahon, Nicholas Timpson, David Evans, Grant Montgomery, Aniket Mishra, Yaxing WangJiejin Wang, E Rochtchina, Ozren Polasek, Alan Wright, Najaf Amin, Elisabeth Van Leeuwen, James Wilson, Craig Pennell, Cornelia van Duijn, Paulus De Jong, Johannes Vingerling, Xin Zhou, Peng Chen, Ruoying Li, Wanting Tay, Yingfeng Zheng, Merwyn Chew, Kathryn Burdon, Jamie Craig, Sudha Iyengar, Robert Igo, Jonathan Lass, Emily Chew, Toomas Haller, Evelin Mihailov, Andres Metspalu, Juho Wedenoja, Claire Simpson, Robert Wojciechowski, Rene Hohn, Alireza Mirshahi, Tanja Zeller, Norbert Pfeiffer, Karl Lackner, Thomas Bettecken, Thomas Meitinger, Konrad Oexle, Mario Pirastu, Laura Portas, Abhishek Nag, Katie Williams, Ekaterina Yonova-Doing, Ronald Klein, Barbara Klein, S Hosseini, Andrew Paterson, Kari Makela, Terho Lehtimaki, Mika Kahonen, Olli Raitakari, Nagahisa Yoshimura, Fumihiko Matsuda, Lijia Chen, Chipui Pang, Sheaping Yip, Maurice Yap, Akira Meguro, Nobuhisa Mizuki, Hidetoshi Inoko, Paul Foster, Jinghua Zhao, Eranga Vithana, E Tai, Qiao Fan, Liang Xu, Harry Campbell, Brian Fleck, Igor Rudan, Tin Aung, Albert Hofman, André Uitterlinden, Goran Bencic, Chiea Khor, Hannah Forward, Olavi Parssinen, Paul Mitchell, Fernando Rivadeneira, Alex Hewitt, Cathy Williams, Ben Oostra, Yikying Teo, Christopher Hammond, Dwight Stambolian, David Mackey, Caroline Klaver, Tienyin Wong, Seangmei Saw, Paul N. Baird

    Research output: Contribution to journalArticlepeer-review

    130 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


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