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

近视的遗传结构及其对风险分层和预后的影响

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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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