title: Coordinated genetic scaling of the human eye: shared determination of axial eye length and corneal curvature.
abstract: OBJECTIVE
  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.
authors: Centre for Myopia Research, School of Optometry, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. jeremy.guggenheim@polyu.edu.hk
authors: Jeremy A
authors: JA
authors: Guggenheim
authors: Xin
authors: X
authors: Zhou
authors: David M
authors: DM
authors: Evans
authors: Nicholas J
authors: NJ
authors: Timpson
authors: George
authors: G
authors: McMahon
authors: John P
authors: JP
authors: Kemp
authors: Beate
authors: B
authors: St Pourcain
authors: Kate
authors: K
authors: Northstone
authors: Susan M
authors: SM
authors: Ring
authors: Qiao
authors: Q
authors: Fan
authors: Tien-Yin
authors: TY
authors: Wong
authors: Ching Yu
authors: CY
authors: Cheng
authors: Chiea Chuen
authors: CC
authors: Khor
authors: Tin
authors: T
authors: Aung
authors: Seang Mei
authors: SM
authors: Saw
authors: Cathy
authors: C
authors: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D058452:Axial Length, Eye / Q000503:physiopathology*; D001827:Body Height / Q000502:physiology*; D003315:Cornea / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012030:Refractive Errors / Q000235:genetics / Q000473:pathology*; D044465:White People
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