Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Nat Genet. 2013 Mar;45(3):314-8. doi: 10.1038/ng.2554. Epub 2013 Feb 10.


Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

Publication types

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

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Asian People / genetics
  • Bone Morphogenetic Protein 2 / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Homeodomain Proteins / genetics
  • Humans
  • KCNQ Potassium Channels / genetics
  • Laminin / genetics
  • Myopia / genetics*
  • Receptors, AMPA / genetics
  • Refractive Errors / genetics*
  • Risk Factors
  • Serine Proteases / genetics
  • Trans-Activators / genetics
  • White People / genetics


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Homeodomain Proteins
  • KCNQ Potassium Channels
  • KCNQ5 protein, human
  • Laminin
  • Receptors, AMPA
  • SIX6 protein, human
  • Trans-Activators
  • glutamate receptor ionotropic, AMPA 4
  • laminin alpha 2
  • Alcohol Oxidoreductases
  • retinol dehydrogenase 5
  • PRSS56 protein, human
  • Serine Proteases

Associated data

  • GEO/GSE20191

Grants and funding