Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci

Hum Genet. 2018 Dec;137(11-12):881-896. doi: 10.1007/s00439-018-1942-8. Epub 2018 Oct 10.


Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10-8) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10-35). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism.

MeSH terms

  • Astigmatism / genetics*
  • Astigmatism / pathology
  • Biological Specimen Banks
  • Cornea / pathology
  • Corneal Diseases / genetics*
  • Corneal Diseases / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Male
  • Middle Aged
  • Myopia / genetics*
  • Myopia / pathology
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Ubiquitin-Protein Ligases
  • United Kingdom
  • White People / genetics


  • Guanine Nucleotide Exchange Factors
  • NPLOC4 protein, human
  • Nuclear Proteins
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases