Skip to content

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

Research output: Contribution to journalArticle

  • The CREAM Consortium
  • the 23 and Me Research Team
  • UK Biobank Eye and Vision Consortium
  • Milly S. Tedja
Original languageEnglish
Pages (from-to)834-848
Number of pages15
JournalNature Genetics
Volume50
Issue number6
Early online date28 May 2018
DOIs
DateAccepted/In press - 22 Jan 2018
DateE-pub ahead of print - 28 May 2018
DatePublished (current) - Jun 2018

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.

Download statistics

No data available

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via nature at http://www.nature.com/articles/s41588-018-0127-7 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF-document

DOI

View research connections

Related faculties, schools or groups