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

Tedja, Milly S; Wojciechowski, Robert; Hysi, Pirro G; Eriksson, Nicholas; Furlotte, Nicholas A; Verhoeven, Virginie J M; Iglesias, Adriana I; Meester-Smoor, Magda A; Tompson, Stuart W; Fan, Qiao; Khawaja, Anthony P; Cheng, Ching-Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost B; ... (2018). Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature genetics, 50(6), pp. 834-848. Springer Nature 10.1038/s41588-018-0127-7

[img] Text
s41588-018-0127-7.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Höhn, René Gerhard Joachim

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1546-1718

Publisher:

Springer Nature

Language:

English

Submitter:

René Gerhard Joachim Höhn

Date Deposited:

21 Oct 2019 15:49

Last Modified:

22 Oct 2019 23:28

Publisher DOI:

10.1038/s41588-018-0127-7

PubMed ID:

29808027

BORIS DOI:

10.7892/boris.134091

URI:

https://boris.unibe.ch/id/eprint/134091

Actions (login required)

Edit item Edit item
Provide Feedback