Five genetic variants near GJD2, RBFOX1, LAMA2, KCNQ5, and LRRC4C exhibit consistent variance heterogeneity in association with refractive error across two independent cohorts totaling over 340,000 individuals, indicating that these loci influence myopia susceptibility through gene-environment interactions rather than simple additive genetic effects.

Spending more time in school reduces time spent outdoors and increases close-up visual tasks, which changes how the retina processes light. This alters signals from specific nerve cells in the eye that control eye growth. Genes that affect how these nerve cells connect, how they pass signals, and how the eye's outer layer stays strong become more active in their negative effects under this visual environment. The eye grows too long as a result, causing distant objects to appear blurry.