Identification of a candidate gene for astigmatism

Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):1260-7. doi: 10.1167/iovs.12-10463.

Abstract

Purpose: Astigmatism is a common refractive error that reduces vision, where the curvature and refractive power of the cornea in one meridian are less than those of the perpendicular axis. It is a complex trait likely to be influenced by both genetic and environmental factors. Twin studies of astigmatism have found approximately 60% of phenotypic variance is explained by genetic factors. This study aimed to identify susceptibility loci for astigmatism.

Methods: We performed a meta-analysis of seven genome-wide association studies that included 22,100 individuals of European descent, where astigmatism was defined as the number of diopters of cylinder prescription, using fixed effect inverse variance-weighted methods.

Results: A susceptibility locus was identified with lead single nucleotide polymorphism rs3771395 on chromosome 2p13.3 (meta-analysis, P = 1.97 × 10(-7)) in the VAX2 gene. VAX2 plays an important role in the development of the dorsoventral axis of the eye. Animal studies have shown a gradient in astigmatism along the vertical plane, with corresponding changes in refraction, particularly in the ventral field.

Conclusions: This finding advances the understanding of refractive error, and provides new potential pathways to be evaluated with regard to the development of astigmatism.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Astigmatism / genetics*
  • Australia
  • Chromosomes, Human, Pair 2*
  • Environment
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Registries / statistics & numerical data
  • United Kingdom
  • Young Adult

Substances

  • Homeodomain Proteins
  • VAX2 protein, human