1. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error
- Author
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Cheng, Ching-Yu, Schache, Maria, Ikram, M Kamran, Young, Terri L, Guggenheim, Jeremy A, Vitart, Veronique, MacGregor, Stuart, Verhoeven, Virginie JM, Barathi, Veluchamy A, Liao, Jiemin, Hysi, Pirro G, Bailey-Wilson, Joan E, St. Pourcain, Beate, Kemp, John P, McMahon, George, Timpson, Nicholas J, Evans, David M, Montgomery, Grant W, Mishra, Aniket, Wang, Ya Xing, Wang, Jie Jin, Rochtchina, Elena, Polasek, Ozren, Wright, Alan F, Amin, Najaf, van Leeuwen, Elisabeth M, Wilson, James F, Pennell, Craig E, van Duijn, Cornelia M, de Jong, Paulus TVM, Vingerling, Johannes R, Zhou, Xin, Chen, Peng, Li, Ruoying, Tay, Wan-Ting, Zheng, Yingfeng, Chew, Merwyn, Error and Myopia, Consortium for Refractive, Cohort, 1958 British Birth, Rahi, Jugnoo S, cohort, Aichi, Yoshimura, Nagahisa, Yamashiro, Kenji, Miyake, Masahiro, ALIENOR, Delcourt, Cécile, Maubaret, Cecilia, ALSPAC, Williams, Cathy, Northstone, Kate, Ring, Susan M, Davey-Smith, George, ANZRAG, Craig, Jamie E, Burdon, Kathryn P, Fogarty, Rhys D, AREDS1a, Iyengar, Sudha K, Igo, Robert P, Chew, Emily, Janmahasathian, Sarayut, AREDS1b, AREDS1c, Stambolian, Dwight, Wilson, Joan E Bailey, BATS, Lu, Yi, Study, Beijing Eye, Jonas, Jost B, Xu, Liang, Saw, Seang-Mei, BMES, Baird, Paul N, Mitchell, Paul, CIEMS, Nangia, Vinay, CROATIA-Korčula, Hayward, Caroline, CROATIA-Split, Campbell, Harry, CROATIA-Vis, Rudan, Igor, Vatavuk, Zoran, DCCT, Paterson, Andrew D, Hosseini, S Mohsen, GWAS, FECD Fuchs Dystrophy, Fondran, Jeremy R, Study, Myopia, Feng, Sheng, and Study, Erasmus Rucphen Family
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Allied Health and Rehabilitation Science ,Health Sciences ,Ophthalmology and Optometry ,Human Genome ,Eye Disease and Disorders of Vision ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Adolescent ,Adult ,Aged ,Asian People ,Axial Length ,Eye ,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 ,White People ,Consortium for Refractive Error and Myopia ,Fuchs' Genetics Multi-Center Study Group ,Wellcome Trust Case Control Consortium 2 ,Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions ,and Complications Research Group ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - 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.
- Published
- 2013