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

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error
Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error
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.
1061-4036
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
et al.
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Carare, Roxana-Octavia and Lotery, Andrew , et al. (2018) Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature Genetics, 50.

Record type: Article

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.

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Published date: 28 May 2018

Identifiers

Local EPrints ID: 421563
URI: https://eprints.soton.ac.uk/id/eprint/421563
ISSN: 1061-4036
PURE UUID: d5019033-ea10-46d6-8f20-1c1862cd315d
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 15 Jun 2018 16:30
Last modified: 15 Mar 2019 01:34

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