Major genetic effects in glaucoma: commingling analysis of optic disc parameters in an older Australian population.
OBJECTIVE
To test the hypothesis that there is a major genetic determinant of vertical disc diameter (VDD) and vertical cup-to-disc ratio (VCDR) in a large, population-based sample.


METHODS
Data were collected from 3654 individuals, 49 years of age or older, participating in the Blue Mountains Eye Study. VDD and VCDR were determined from stereo optic disc photographs. Commingling analyses in SKUDRIVER/SKUMIX were performed in nonglaucomatous eyes to investigate whether the observed VDD and VCDR data were best described by a one-, two-, or three-distribution model.


RESULTS
VDD data did not show evidence of commingling. After adjustment for the effects of age, VDD and intraocular pressure, the best model for VCDR consisted of a mixture of three distributions in Hardy-Weinberg equilibrium. The proportion of the variance in VCDR explained by this mixing component was 0.58.


CONCLUSIONS
Findings from this study are consistent with the presence of a major gene that accounts for 58% of the variance in VCDR. These results strongly support further efforts to identify the genetic variants responsible for this quantitative trait, which is a key constituent of the phenotype of primary open-angle glaucoma (POAG).
van Koolwijk
Leonieke M E
LM
Glaucoma Service, Moorfields Eye Hospital, London, United Kingdom. l.vankoolwijk@oogziekenhuis.nl
Healey
Paul R
PR
Hitchings
Roger A
RA
Mitchell
Paul
P
Sham
Pak C
PC
McGuffin
Peter
P
Viswanathan
Ananth C
AC
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000235:genetics*; D014065:Tonometry, Ocular