@article{953d827b053e4d349b0f9f3048484767,
title = "Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error",
abstract = "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.",
author = "CREAM and {23andMe Research Team} and {UK Biobank Eye and Vision Consortium} and Tedja, {Milly S.} and Robert Wojciechowski and Hysi, {Pirro G.} and Nicholas Eriksson and Furlotte, {Nicholas A.} and Verhoeven, {Virginie J.M.} and Iglesias, {Adriana I.} and Meester-Smoor, {Magda A.} and Tompson, {Stuart W.} and Qiao Fan and Khawaja, {Anthony P.} and Cheng, {Ching Yu} and Ren{\'e} H{\"o}hn and Kenji Yamashiro and Adam Wenocur and Clare Grazal and Toomas Haller and Andres Metspalu and Juho Wedenoja and Jonas, {Jost B.} and Wang, {Ya Xing} and Jing Xie and Paul Mitchell and Foster, {Paul J.} and Klein, {Barbara E.K.} and Ronald Klein and Paterson, {Andrew D.} and Hosseini, {S. Mohsen} and Shah, {Rupal L.} and Cathy Williams and Teo, {Yik Ying} and Tham, {Yih Chung} and Preeti Gupta and Wanting Zhao and Yuan Shi and Saw, {Woei Yuh} and Tai, {E. Shyong} and Sim, {Xue Ling} and Huffman, {Jennifer E.} and Ozren Pola{\v s}ek and Caroline Hayward and Goran Bencic and Igor Rudan and Wilson, {James F.} and Tin Aung and Evans, {David M.} and Kemp, {John P.} and Smith, {George D.} and David Crabb and Emanuele Trucco and Klaver, {Caroline C. W.}",
note = "Funding for this particular GWAS mega-analysis was provided by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme (grant 648268), the Netherlands Organisation for Scientific Research (NWO, grant 91815655) and the National Eye Institute (grant R01EY020483). ",
year = "2018",
month = jun,
day = "1",
doi = "10.1038/s41588-018-0127-7",
language = "English",
volume = "50",
pages = "834--848",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "6",
}