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.

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Persistent URL dx.doi.org/10.1038/s41588-018-0127-7, hdl.handle.net/1765/107321
Journal Nature Genetics
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Citation
Tedja, M, Wojciechowski, R, Hysi, P.G, Eriksson, N. (Nicholas), Furlotte, N.A. (Nicholas A.), Verhoeven, V.J.M, … Klaver, C.C.W. (2018). Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature Genetics, 1–15. doi:10.1038/s41588-018-0127-7