A1 Journal article – refereed
Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

List of Authors: Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, MacGregor S, Verhoeven VJM, Barathi VA, Liao JM, 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 RY, Tay WT, Zheng YF, 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, Hohn 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, Parssinen O, Mitche 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
Publisher: CELL PRESS
Publication year: 2013
Journal: American Journal of Human Genetics
Journal acronym: AM J HUM GENET
Number in series: 2
Volume number: 93
Issue number: 2
Number of pages: 14
ISSN: 0002-9297

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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Last updated on 2019-03-09 at 17:48