Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.
Nature genetics 2017 ; 50: 834-848.
Wojciechowski R, Hysi PG, Eriksson N, Furlotte NA, Khawaja AP, Cheng CY, Höhn R, Yamashiro K, Haller T, Metspalu A, Wedenoja J, Jonas JB, Wang YX, Mitchell P, Foster PJ, Klein R, Paterson AD, Hosseini SM, Williams C, Teo YY, Tham YC, Gupta P, Zhao W, Tai ES, Huffman JE, Polasek O, Hayward C, Rudan I, Wilson JF, Joshi PK, Zeller T, van Leeuwen EM, Iyengar SK, Lass JH, Hofman A, Rivadeneira F, Uitterlinden AG, Vingerling JR, Lehtimäki T, Raitakari OT, Biino G, Concas MP, Schwantes-An TH, Igo RP, Cuellar-Partida G, Martin NG, Craig JE, Gharahkhani P, Williams KM, Rahi JS, Delcourt C, Bellenguez C, Ried JS, Meitinger T, Gieger C, Wong TY, Hewitt AW, Mackey DA, Simpson CL, Pfeiffer N, Pärssinen O, Baird PN, Vitart V, Amin N, van Duijn CM, Young TL, Saw SM, Stambolian D, MacGregor S, Guggenheim JA, Tung JY, and Hammond CJ
DOI : 10.1038/s41588-018-0127-7
PubMed ID : 29808027
PMCID : PMC5980758
Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.