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

Nat Genet. 2018 Jun;50(6):834-848. doi: 10.1038/s41588-018-0127-7. Epub 2018 May 28.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics
  • Blindness / genetics
  • Blindness / metabolism
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods
  • Humans
  • Male
  • Myopia / genetics
  • Polymorphism, Single Nucleotide
  • Refractive Errors / genetics*
  • Refractive Errors / metabolism
  • Retina / metabolism
  • Retinal Pigment Epithelium / metabolism
  • Signal Transduction