TY - JOUR
T1 - Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error
AU - Cheng, Ching-Yu
AU - Schache, Maria
AU - Ikram, M. Kamran
AU - Young, Terri L.
AU - Guggenheim, Jeremy A.
AU - Vitart, Veronique
AU - MacGregor, Stuart
AU - Verhoeven, Virginie J. M.
AU - Barathi, Veluchamy A.
AU - Liao, Jiemin
AU - Hysi, Pirro G.
AU - Bailey-Wilson, Joan E.
AU - St Pourcain, Beate
AU - Kemp, John P.
AU - McMahon, George
AU - Timpson, Nicholas J.
AU - Evans, David M.
AU - Montgomery, Grant W.
AU - Mishra, Aniket
AU - Wang, Ya Xing
AU - Wang, Jie Jin
AU - Rochtchina, Elena
AU - Polasek, Ozren
AU - Wright, Alan F.
AU - Amin, Najaf
AU - van Leeuwen, Elisabeth M.
AU - Wilson, James F.
AU - Pennell, Craig E.
AU - van Duijn, Cornelia M.
AU - de Jong, Paulus T. V. M.
AU - Vingerling, Johannes R.
AU - Zhou, Xin
AU - Chen, Peng
AU - Li, Ruoying
AU - Tay, Wan-Ting
AU - Zheng, Yingfeng
AU - Chew, Merwyn
AU - Burdon, Kathryn P.
AU - Craig, Jamie E.
AU - Iyengar, Sudha K.
AU - Igo, Robert P.
AU - Lass, Jonathan H.
AU - Chew, Emily Y.
AU - Haller, Toomas
AU - Mihailov, Evelin
AU - Metspalu, Andres
AU - Nag, Abhishek
AU - Williams, Katherine
AU - Hammond, Christopher J.
AU - Consortium Refractive Error Myopia
AU - Fuchs Genetics Multictr Study Grp
AU - Wellcome Trust Case Control Consor
AU - Diabet Control Complications Trial
AU - Plomin, Robert
PY - 2013/8/8
Y1 - 2013/8/8
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Asian Continental Ancestry Group
KW - Axial Length, Eye
KW - European Continental Ancestry Group
KW - Eye Proteins
KW - Female
KW - Gene Expression
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Refractive Errors
KW - Signal Transduction
U2 - 10.1016/j.ajhg.2013.06.016
DO - 10.1016/j.ajhg.2013.06.016
M3 - Article
C2 - 24144296
SN - 0002-9297
VL - 93
SP - 264
EP - 277
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -
