Genome-wide association analyses identify new loci influencing intraocular pressure

Hum Mol Genet. 2018 Jun 15;27(12):2205-2213. doi: 10.1093/hmg/ddy111.


Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, the leading cause of irreversible blindness worldwide. While previous studies have identified numerous genetic variants associated with IOP, these loci only explain a fraction of IOP heritability. Recently established of biobank repositories have resulted in large amounts of data, enabling the identification of the remaining heritability for complex traits. Here, we describe the largest genome-wide association study of IOP to date using participants of European ancestry from the UK Biobank. We identified 671 directly genotyped variants that are significantly associated with IOP (P < 5 × 10-8). In addition to 103 novel loci, the top ranked novel IOP genes are LMX1B, NR1H3, MADD and SEPT9. We replicated these findings in an external population and examined the pleiotropic nature of these loci. These discoveries not only further our understanding of the genetic architecture of IOP, but also shed new light on the biological processes underlying glaucoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Glaucoma / genetics*
  • Glaucoma / physiopathology
  • Humans
  • Intraocular Pressure / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Septins / genetics
  • Tonometry, Ocular
  • White People


  • SEPTIN9 protein, human
  • Septins