The MAGIC Cohort Study: Genetic Associations of Anisometropia in Chinese Population.

Myopia, particularly high myopia (HM), represents a critical global public health issue due to its strong association with irreversible visual impairment. While past genetic studies have identified numerous myopia-associated loci, they explain only a modest proportion of its heritability. To address this gap, we established the Myopia Associated Genetics and Intervention Consortium (MAGIC) cohort, the first large-scale whole-exome sequencing (WES) cohort dedicated to the Chinese myopia population, which has already unveiled HM-associated genes, novel rare-variant mechanisms, and open-access analytic tools. The cohort was established in Wenzhou, China, in May 2019 and comprises three phases. Phase I (n = 9696) enrolled extreme, early-onset HM adolescents; Phases II (n = 9368) and III (n = 3544; ongoing recruitment) include young adults and elders, enabling comparison and replication of genetic findings. Longitudinal data from electronic medical records (EMRs) for 2566 individuals further support progression analysis. Here, we extend the MAGIC resource to dissect the genetic basis of myopia-related anisometropia. We discovered novel association signals for spherical-equivalent anisometropia in HM adolescents, including SNP rs61758755 in RAD23B (β = 0.72, P = 1.50 × 10-9) and SNP rs59002125 in ABCC6 (β = 0.69, P = 8.86 × 10-8). We also identified 26 suggestive variants linked to anisometropia and its progression. Together, these findings underscore the value of large-scale WES in detecting functional risk alleles and provide foundational insights into the genetic architecture of myopia and its relevant refractive error. The MAGIC cohort serves as a valuable foundation for future mechanistic studies.