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

Jeremy A Guggenheim, Xin Zhou, David M Evans, Nicholas J Timpson, George McMahon, John P Kemp, Beate St Pourcain, Kate Northstone, Susan M Ring, Qiao Fan, Tien-Yin Wong, Ching Yu Cheng, Chiea Chuen Khor, Tin Aung, Seang Mei Saw, Cathy Williams

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)


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, h(2) = 0.46 (SE = 0.16, P = 0.002); corneal curvature, h(2) = 0.42 (SE = 0.16, P = 0.004); height, h(2) = 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.

Original languageEnglish
Pages (from-to)1715-21
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number3
Publication statusPublished - Mar 2013


  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group
  • Axial Length, Eye
  • Body Height
  • Cornea
  • Cross-Sectional Studies
  • European Continental Ancestry Group
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Refractive Errors


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