Automated quantification of inherited phenotypes from color images: a twin study of the variability of optic nerve head shape

Abstract

Purpose. Discovery and description of heritable optic nerve head (ONH) phenotypes have been haphazard. In this preliminary study, the authors test the hypothesis that inheritable phenotypes can be discovered and quantified computationally by estimating three-dimensional ONH shape parameters from stereo color photographs from the Twins Eye Study in Tasmania and determining how much of the variability in ONH shape is accounted for by genetic influence.

Methods. Three-dimensional ONH shape was estimated by an automated algorithm from stereoscopic optic disc color photographs of a random sample of 172 subjects (344 eyes, 45 pairs of monozygotic [MZ] and 41 dizygotic [DZ] twins). Shape resemblances between eyes were quantified with a distance metric. The heritability of the shape resemblance was determined both through the distribution of the discongruence indices and through structural equation modeling techniques (ACE model).

Results. Significantly different discongruence indices were found for MZ (1.0286; 95% CI, 0.9872–1.0701) and DZ twins (1.4218; 95% CI, 1.2631–1.5804); larger indices for DZ twins indicated that variability was substantially determined by genetic factors. The standardized variances of the A(dditive genetic), C(ommon environmental), and (nonshared) E(nvironmental) components were 0.80, 2.00 × 10−15 and 0.20, respectively, for all OD, and 0.79, 3.24 × 10−14, and 0.21 for all OS.

Conclusions. This preliminary study shows that quantitative phenotyping of the ONH shape from color images leads to phenotypes that can be measured and are largely under genetic control. The association of these inherited phenotypes with genotypes deserves confirmation and further study.