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

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

Research output: Contribution to journalReview articlepeer-review

207 Citations (Scopus)


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
Pages (from-to)834-850
Number of pages17
JournalNature Genetics
Publication statusPublished - 1 Jun 2018


  • Meta-analysis
  • light-induced signalling
  • genomics
  • refractive error
  • genetics


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