Polygenic risk score for myopia prediction and risk stratification in Chinese children

Aims To assess a polygenic risk score (PRS) for myopia prediction and risk stratification in Chinese children. Methods This study included 4750 children aged 6 to 9 years from the Shanghai Time Outside to Reduce Myopia trial. A weighted PRS comprising 51 single nucleotide polymorphisms was constructed from East Asian ancestry genome-wide association study summary statistics (n=121 172). Linear regression estimated the variance in spherical equivalent (SE) and axial length (AL), explained by the PRS, and the area under the receiver operating characteristic curve (AUC) quantified predictive accuracy for myopia. Results The participants had a mean age of 7.26±0.59 years (boys, 52.8%), and 8.2% had myopia. The incremental adjusted R² values for SE and AL were small for PRS (1.7% and 0.3%) and parental myopia (2.5% and 0.5%). Combining PRS with parental myopia modestly increased the incremental adjusted R² to 4.0% and 0.8%. The combined model yielded AUCs of 0.719 (95% CI, 0.694 to 0.744), 0.709 (95% CI, 0.683 to 0.736) and 0.861 (95% CI, 0.791 to 0.930) for overall, low and moderate myopia, respectively, exceeding those of models with PRS or parental myopia alone. Compared with the remaining children, those in the highest 25%, 10% and 5% of the PRS distribution had 1.52, 1.63 and 1.88 times higher odds of myopia, respectively. Conclusions PRS may help identify children at high risk of myopia, particularly in combination with parental myopia. Its incremental contribution remains limited, and further longitudinal studies and external validation are needed to evaluate its clinical value.