Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

Nat Genet. 2013 Feb;45(2):155-63. doi: 10.1038/ng.2506. Epub 2013 Jan 6.

Abstract

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Publication types

  • Meta-Analysis

MeSH terms

  • Asian Continental Ancestry Group / genetics
  • Cornea / anatomy & histology*
  • Corneal Pachymetry
  • European Continental Ancestry Group / genetics
  • Fibronectins / genetics*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics*
  • Genetic Loci / genetics*
  • Genome-Wide Association Study
  • Glaucoma / genetics
  • Humans
  • Keratoconus / genetics*
  • Microarray Analysis
  • Odds Ratio
  • Real-Time Polymerase Chain Reaction

Substances

  • FNDC3B protein, human
  • FOXO1 protein, human
  • Fibronectins
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors

Supplementary concepts

  • Glaucoma 1, Open Angle, O