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Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.

Accepted version
Peer-reviewed

Type

Article

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Authors

Wojciechowski, Robert 
Eriksson, Nicholas 
Furlotte, Nicholas A 

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.

Description

Keywords

Adult, Asian People, Blindness, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Myopia, Polymorphism, Single Nucleotide, Refractive Errors, Retina, Retinal Pigment Epithelium, Signal Transduction, White People

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

50

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13048)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
TCC (None)