title: Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
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.
authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore; Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D058452:Axial Length, Eye / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012030:Refractive Errors / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D044465:White People
chemical_list: D005136:Eye Proteins