Genome-wide association study in Asians identifies novel loci for high myopia and highlights a nervous system role in its pathogenesis

Abstract Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14,096 samples from East and Southeast Asian populations (2,549 patients with high myopia and 11,547 healthy controls). Methods We performed a GWAS in 3,269 Japanese individuals (1,668 high myopia cases and 1,601 controls), followed by replication analysis in a total of 10,827 additional samples (881 high myopia cases and 9,946 controls) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified nine loci with genome-wide significance (P Conclusions The current study identified six novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the etiology and pathophysiology of myopia at the molecular level.