SCIENCE@home

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

Yu Huang,C. Kee,P. Hocking,Cathy Williams,S.P. Yip,J. Guggenheim

Published 2019 in Investigative Ophthalmology and Visual Science

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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-50 of 50 references · Page 1 of 1

CITED BY

Showing 1-11 of 11 citing papers · Page 1 of 1