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

CREAM, 23andMe Research Team, UK Biobank Eye and Vision Consortium

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)834-848
Number of pages15
JournalNature Genetics
Volume50
Issue number6
DOIs
StatePublished - Jun 1 2018

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Refractive Errors
Genome-Wide Association Study
Meta-Analysis
Light
Retina
Cell Physiological Phenomena
Vertebrate Photoreceptor Cells
Sclera
Retinal Pigment Epithelium
Myopia
Vascular Endothelium
Blindness
Synaptic Transmission
Computer Simulation
Extracellular Matrix
RNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. / CREAM; 23andMe Research Team; UK Biobank Eye and Vision Consortium.

In: Nature Genetics, Vol. 50, No. 6, 01.06.2018, p. 834-848.

Research output: Contribution to journalArticle

CREAM, 23andMe Research Team & UK Biobank Eye and Vision Consortium 2018, 'Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error', Nature Genetics, vol. 50, no. 6, pp. 834-848. https://doi.org/10.1038/s41588-018-0127-7
CREAM ; 23andMe Research Team ; UK Biobank Eye and Vision Consortium. / Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. In: Nature Genetics. 2018 ; Vol. 50, No. 6. pp. 834-848.
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