Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology.
OBJECTIVE
The genetic etiology of primary open-angle glaucoma (POAG) is still largely unknown, because of its complexity and disparities in its classification. This study was undertaken to determine the genetic contribution to various early, continuous markers of POAG by assessing the heritability of intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim and optic disc parameters in a genetically isolated population.


METHODS
A total of 2620 subjects (mean age, 48 years; range 18-86) from extended pedigrees living in a small town in The Netherlands underwent an extensive ophthalmic examination. Their IOP was measured by Goldmann applanation tonometry, their RNFL thickness by scanning laser polarimetry (GDx VCC), and their optic disc parameters by confocal scanning laser ophthalmoscopy (HRT II). Risk associations were explored by linear regression analyses and heritability estimates by variance component methods.


RESULTS
Inbreeding was present in 2042 (81%) participants, and was significantly associated with a higher IOP (P < 0.001). The heritability estimate for IOP was 0.35 (95% confidence interval [CI], 0.27-0.43); for RNFL thickness, 0.48 (95% CI, 0.35-0.60); and for neuroretinal rim area, 0.39 (95% CI, 0.20-0.58). Nongenetic factors accounted for only a small proportion (<or=0.13) of the variance in all three traits.


CONCLUSIONS
Early, continuous markers of POAG are strongly determined by additive genetic effects. The results support a quantitative trait linkage strategy to discover new genes for POAG.
van Koolwijk
Leonieke M E
LM
Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands. koolwijk@oogziekenhuis.nl
Despriet
Dominiek D G
DD
van Duijn
Cornelia M
CM
Pardo Cortes
Luba M
LM
Vingerling
Johannes R
JR
Aulchenko
Yurii S
YS
Oostra
Ben A
BA
Klaver
Caroline C W
CC
Lemij
Hans G
HG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009426:Netherlands; D009898:Optic Disk / Q000473:pathology*; D019655:Quantitative Trait, Heritable; D012165:Retinal Ganglion Cells / Q000473:pathology* / Q000648:ultrastructure