Commingling analysis of intraocular pressure and glaucoma in an older Australian population.
OBJECTIVE
To test the hypothesis of a major genetic determinant of intraocular pressure (IOP) under the mixed genetic model in a defined population, and to elucidate the relationship between IOP and glaucoma.


METHODS
IOP was measured in 3654 persons attending the Blue Mountains Eye Study. A commingling analysis on IOP was performed using a new program, SKUDRIVER. The goodness of fit of 1-, 2- and 3-distribution models was measured. This was repeated after the glaucoma cases had been removed from the dataset, and further repeated on the glaucoma cases in the dataset.


RESULTS
The best model was 3-distribution with no evidence for Hardy-Weinberg disequilibrium. The proportion of variance explained by this major effect was 0.18. When glaucoma cases were removed, the best model had 2 distributions. There was no evidence of admixture in glaucoma patients.


CONCLUSIONS
The findings of this study are consistent with the presence of a major gene accounting for 18% of the variance of IOP, which could therefore influence the risk of glaucoma, in this population. These findings suggest methods of optimizing strategies for family and association studies to identify quantitative trait loci for IOP. No evidence for distinct IOP-dependent and IOP-independent subgroups of glaucoma was found.
Viswanathan
Ananth C
AC
Moorfields Eye Hospital, London, United Kingdom. a.viswanathan@ucl.ac.uk
Hitchings
Roger A
RA
Indar
Andrea
A
Mitchell
Paul
P
Healey
Paul R
PR
McGuffin
Peter
P
Sham
Pak C
PC
D000328:Adult; D000375:Aging; D001315:Australia; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005901:Glaucoma / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D008962:Models, Theoretical; D010375:Pedigree; D012307:Risk Factors