Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree

Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3723-9. doi: 10.1167/iovs.05-0312.


Purpose: The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype.

Methods: Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals.

Results: Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci.

Conclusions: Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 10 / genetics*
  • Cytoskeletal Proteins / genetics
  • Eye Proteins / genetics
  • Female
  • Genetic Linkage*
  • Genotype
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / physiopathology
  • Glycoproteins / genetics
  • Humans
  • Intraocular Pressure / genetics*
  • Lod Score
  • Male
  • Middle Aged
  • Optic Disk / pathology*
  • Pedigree
  • Phenotype


  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • trabecular meshwork-induced glucocorticoid response protein