Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree.
OBJECTIVE
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.
Charlesworth
Jac C
JC
Menzies Research Institute, University of Tasmania, Hobart, Australia.
Dyer
Thomas D
TD
Stankovich
Jim M
JM
Blangero
John
J
Mackey
David A
DA
Craig
Jamie E
JE
Green
Catherine M
CM
Foote
Simon J
SJ
Baird
Paul N
PN
Sale
Michèle M
MM
D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000473:pathology*; D010375:Pedigree; D010641:Phenotype; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin