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

, Yu Huang, Chea-Su Kee, Paul M. Hocking, Cathy Williams, Shea Ping Yip, Jeremy A. Guggenheim

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    12 Citations (Scopus)
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    PURPOSE. The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G X E) interactions in myopia susceptibility. Few such G X 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 X 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 X 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 & Visual Science
    Issue number2
    Publication statusPublished - 1 Feb 2019


    • Alspac
    • Genome-wide association study
    • Myopia
    • Refractive error
    • Uk biobank

    ASJC Scopus subject areas

    • Ophthalmology
    • Sensory Systems
    • Cellular and Molecular Neuroscience


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