Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density

Nat Commun. 2019 Mar 20;10(1):1284. doi: 10.1038/s41467-019-09304-9.

Abstract

The corneal endothelium is vital for transparency and proper hydration of the cornea. Here, we conduct a genome-wide association study of corneal endothelial cell density (cells/mm2), coefficient of cell size variation (CV), percentage of hexagonal cells (HEX) and central corneal thickness (CCT) in 6,125 Icelanders and find associations at 10 loci, including 7 novel. We assess the effects of these variants on various ocular biomechanics such as corneal hysteresis (CH), as well as eye diseases such as glaucoma and corneal dystrophies. Most notably, an intergenic variant close to ANAPC1 (rs78658973[A], frequency = 28.3%) strongly associates with decreased cell density and accounts for 24% of the population variance in cell density (β = -0.77 SD, P = 1.8 × 10-314) and associates with increased CH (β = 0.19 SD, P = 2.6 × 10-19) without affecting risk of corneal diseases and glaucoma. Our findings indicate that despite correlations between cell density and eye diseases, low cell density does not increase the risk of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics*
  • Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism
  • Case-Control Studies
  • Cell Count
  • Cell Size
  • Corneal Dystrophies, Hereditary / diagnosis
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / pathology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Endothelium, Corneal / metabolism*
  • Endothelium, Corneal / pathology
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Genetic Loci
  • Genome-Wide Association Study
  • Glaucoma / diagnosis
  • Glaucoma / genetics*
  • Glaucoma / pathology
  • Humans
  • Intraocular Pressure
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Whole Genome Sequencing

Substances

  • ANAPC1 protein, human
  • Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome