Genetic Architecture of Myopia and Its Implications for Risk Stratification and Prognosis

TL;DR

This paper explores the genetic basis of myopia and how it can help predict and manage the condition more effectively.

Contribution

The paper presents a multilayered genetic framework for myopia, integrating polygenic and rare variant analyses for risk stratification.

Findings

Myopia-related genetic variants are enriched in pathways affecting retinal responses to visual and metabolic stimuli.

Polygenic risk scores can quantify genetic susceptibility for population-level risk assessment.

Early-onset high myopia overlaps with inherited retinal and syndromic disorders.

Abstract

Myopia is a prevalent ocular condition with marked heterogeneity in onset and progression. Although diagnosis is straightforward, predicting disease trajectories and identifying risks of high or pathologic myopia remain main clinical challenges. Advances in human genetics have substantially reshaped current understanding of myopia, revealing a complex architecture involving common polygenic susceptibility, rare high-impact variants, and cumulative genetic risk burden. Large-scale genome-wide association studies demonstrate that myopia-related variants are enriched in regulatory and signaling pathways that modulate retinal neuronal and glial responses to visual and metabolic stimuli, while exome sequencing studies highlight overlap between early-onset high myopia and inherited retinal or syndromic disorders. Polygenic risk scores further translate common-variant burden into quantitative measures of genetic susceptibility, enabling population-level risk stratification and early risk assessment, albeit with performance differences across ancestries and clinical outcomes. Together, these findings delineate a multilayered genetic framework for myopia and support the role of genetic information as a complementary component of prognostic assessment. Integration of genetic data with longitudinal clinical and environmental information may further improve the prediction of myopia trajectories and facilitate more individualized management strategies.

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