A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia

Yu Huang, Chea-su Kee, Paul M. Hocking, Cathy E M Williams, Shea Ping Yip, Jeremy Guggenheim, UK Biobank Eye and Vision Consortium, The CREAM Consortium

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
198 Downloads (Pure)

Abstract

Purpose: The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G × E) interactions in myopia susceptibility. Few such G × E interactions have been discovered to date. We aimed to test the hypothesis that genetic analysis of susceptibility to visual experience-induced myopia in an animal model would identify novel G × E interaction loci. Methods: Chicks aged 7 days (n = 987) were monocularly deprived of form vision for 4 days. A genome-wide association study (GWAS) was carried out in the 20% of chicks most susceptible and least susceptible to form deprivation (n = 380). There were 304,963 genetic markers tested for association with the degree of induced axial elongation in treated versus control eyes (A-scan ultrasonography). A GWAS candidate region was examined in the following three human cohorts: CREAM consortium (n = 44,192), UK Biobank (n = 95,505), and Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4989). Results: A locus encompassing the genes PIK3CG and PRKAR2B was genome-wide significantly associated with myopia susceptibility in chicks (lead variant rs317386235, P = 9.54e-08). In CREAM and UK Biobank GWAS datasets, PIK3CG and PRKAR2B were enriched for strongly-associated markers (meta-analysis lead variant rs117909394, P = 1.7e-07). In ALSPAC participants, rs117909394 had an age-dependent association with refractive error (-0.22 diopters [D] change over 8 years, P = 5.2e-04) and nearby variant rs17153745 showed evidence of a G × E interaction with time spent reading (effect size -0.23 D, P = 0.022). Conclusions: This work identified the PIK3CG-PRKAR2B locus as a mediator of susceptibility to visually induced myopia in chicks and suggests a role for this locus in conferring susceptibility to myopia in human cohorts.

Original languageEnglish
Pages (from-to)559-569
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume60
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • Refractive error
  • Myopia
  • Genome-wide association study
  • UK Biobank
  • ALSPAC

Fingerprint Dive into the research topics of 'A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia'. Together they form a unique fingerprint.

  • Cite this

    Huang, Y., Kee, C., Hocking, P. M., Williams, C. E. M., Yip, S. P., Guggenheim, J., UK Biobank Eye and Vision Consortium, & The CREAM Consortium (2019). A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia. Investigative Ophthalmology and Visual Science, 60(2), 559-569. https://doi.org/10.1167/iovs.18-25597