Genome-wide association study of myopia progression in Chinese adolescents and application of polygenic risk score prediction.

In recent years, the prevalence of myopia has sharply increased in East Asia, emerging as a major public health issue. This study aimed to identify genetic risk factors for myopia progression and to develop polygenic risk score (PRS) models to predict myopia progression risk. Genotyping was performed using the Asian Screening Array chip among 294 Chinese adolescents who completed a 2-year follow-up. A two-stage (discovery cohort: N = 176; replication cohort: N = 118) genome-wide association study (GWAS) was subsequently conducted. Functional annotation and MAGMA analysis were performed to confirm biological relevance of the identified loci in the progression of myopia. Based on GWAS results from the discovery cohort and a European population from the United Kingdom Biobank (N = 460,536), we constructed single-ancestry and cross-ancestry PRS models with PRSice-2 and PRS-CSx. We evaluated the predictive performance of these models using the replication cohort. Our meta-analysis identified seven novel suggestive loci associated with myopia progression, including FSTL5 on 4q32.2, SMARCA2 on 9p24.3, CCDC3 on 10p13, GALNT6/ACVR1B on 12q13.13, CRY1 on 12q23.3, ULK2 on 17p11.2, and MYL4/EFCAB13-DT on 17q21.32. For myopia progression risk prediction in East Asians, PRS analysis showed that the East Asian training dataset (R 2: 5.69%; OR: 1.61, 95% CI: 1.06-2.44; AUC: 0.66) outperformed both the European and cross-ancestry datasets. This study identified seven promising loci associated with myopia progression and demonstrated that PRS exhibited enhanced predictive performance in genetically and phenotypically matched populations. Our findings expand the genetic understanding of myopia progression in East Asian adolescents and provide new insights for myopia prevention and control.