Coordinated genetic scaling of the human eye: Shared determination of axial eye length and corneal curvature

Guggenheim, J. A., Zhou, X., Evans, D. M., Timpson, N. J., McMahon, G., Kemp, J. P., Pourcain, B. S., Northstone, K., Ring, S. M., Fan, Q., Wong, T. -Y., Cheng, C. Y., Khor, C. C., Aung, T., Saw, S. M. and Williams, C. (2013) Coordinated genetic scaling of the human eye: Shared determination of axial eye length and corneal curvature. Investigative Ophthalmology and Visual Science, 54 3: 1715-1721. doi:10.1167/iovs.12-10560

Author Guggenheim, J. A.
Zhou, X.
Evans, D. M.
Timpson, N. J.
McMahon, G.
Kemp, J. P.
Pourcain, B. S.
Northstone, K.
Ring, S. M.
Fan, Q.
Wong, T. -Y.
Cheng, C. Y.
Khor, C. C.
Aung, T.
Saw, S. M.
Williams, C.
Title Coordinated genetic scaling of the human eye: Shared determination of axial eye length and corneal curvature
Journal name Investigative Ophthalmology and Visual Science   Check publisher's open access policy
ISSN 0146-0404
Publication date 2013-03-01
Year available 2013
Sub-type Article (original research)
DOI 10.1167/iovs.12-10560
Open Access Status DOI
Volume 54
Issue 3
Start page 1715
End page 1721
Total pages 7
Place of publication Rockville, United States
Publisher Association for Research in Vision and Ophthalmology
Language eng
Formatted abstract
Purpose. To examine the extent to which the two major determinants of refractive error, corneal curvature and axial length, are scaled relative to one another by shared genetic variants, along with their relationship to the genetic scaling of height.
Methods. Corneal curvature, axial length, and height were measured in unrelated 14- to 17-year-old white European participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 1915) and in unrelated 40- to 80-year-old participants of the Singapore Chinese Eye Study (SCES; n = 1642). Univariate and bivariate heritability analyses were performed with methods that avoid confounding by common family environment, using information solely from genome-wide high-density genotypes.
Results. In ALSPAC subjects, axial length, corneal curvature, and height had similar lower-bound heritability estimates: axial length, h2 = 0.46 (SE = 0.16, P = 0.002); corneal curvature, h2 = 0.42 (SE = 0.16, P = 0.004); height, h2 = 0.48 (SE = 0.17, P = 0.002). The corresponding estimates in the SCES were 0.79 (SE = 0.18, P < 0.001), 0.35 (SE = 0.20, P = 0.036), and 0.31 (SE = 0.20, P = 0.061), respectively. The genetic correlation between corneal curvature and axial length was 0.69 (SE = 0.17, P = 0.019) for ALSPAC participants and 0.64 (SE = 0.22, P = 0.003) for SCES participants. In the subset of 1478 emmetropic ALSPAC individuals, the genetic correlation was 0.85 (SE = 0.12, P = 0.008).
Conclusions. These results imply that coordinated scaling of ocular component dimensions is largely achieved by hundreds to thousands of common genetic variants, each with a small pleiotropic effect. Furthermore, genome-wide association studies (GWAS) for either axial length or corneal curvature are likely to identify variants controlling overall eye size when using discovery cohorts dominated by emmetropes, but trait-specific variants in discovery cohorts dominated by ametropes.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
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