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.
Duke Scholars
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- White People
- Signal Transduction
- Retinal Pigment Epithelium
- Retina
- Refractive Errors
- Polymorphism, Single Nucleotide
- Myopia
- Male
- Humans
- Genome-Wide Association Study
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- White People
- Signal Transduction
- Retinal Pigment Epithelium
- Retina
- Refractive Errors
- Polymorphism, Single Nucleotide
- Myopia
- Male
- Humans
- Genome-Wide Association Study