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

77 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