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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cheng, C-Y; 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, W-T; Zheng, Y; Chew, M; Consortium for Refractive Error and Myopia, ; Burdon, KP; Craig, JE; Iyengar, SK; Igo, RP; Lass, JH; Fuchs' Genetics Multi-Center Study Group, ; Chew, EY; Haller, T; Mihailov, E; Metspalu, A; Wedenoja, J; Simpson, CL; Wojciechowski, R; Höhn, R; Mirshahi, A; Zeller, T; Pfeiffer, N; Lackner, KJ; Wellcome Trust Case Control Consortium 2, ; 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; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions, and Complications Research Group, ; Makela, K-M; 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, E-S; Fan, Q; Xu, L; Campbell, H; Fleck, B; Rudan, I; Aung, T; Hofman, A; Uitterlinden, AG; Bencic, G; Khor, C-C; Forward, H; Pärssinen, O; Mitchell, P; Rivadeneira, F; Hewitt, AW; Williams, C; Oostra, BA; Teo, Y-Y; Hammond, CJ; Stambolian, D; Mackey, DA; Klaver, CCW; Wong, T-Y; Saw, S-M; Baird, PN

Published Date

  • August 8, 2013

Published In

Volume / Issue

  • 93 / 2

Start / End Page

  • 264 - 277

PubMed ID

  • 24144296

Pubmed Central ID

  • PMC3772747

Electronic International Standard Serial Number (EISSN)

  • 1537-6605

Digital Object Identifier (DOI)

  • 10.1016/j.ajhg.2013.06.016


  • eng

Conference Location

  • United States