Identification of risk genes and biological pathways influencing myopia via transcriptome association study and biomedical ontology methods.

Refractive error remains one of the most common eye diseases in the world, which causes great burden on public health and economy every year. Although genome-wide association studies (GWAS) have identified susceptibility loci for refractive error, the credible causal genes associated with gene expression in brain are still unclear. In addition, the influence of RNA splicing events on refractive error in brain remains unknown. Here, we identified candidate refractive error gene targets and biological pathways. In stage 1, we carried out gene-based association analysis to identify refractive error risk genes. In stage 2, by using transcriptome-wide association studies (TWAS) and colocalization analysis, we identified cis-regulated genes in brain tissues that were positively related to refractive error from the whole gene region and the exon region after RNA splicing, respectively. In stage 3, we reveal biological pathways influencing refractive error using biological ontology and knowledge base methods. We identified 367 risk genes passed gene-based association test. A total of 43 genes in brain could be considered as causal genes using TWAS and colocalization analysis, and 27 were novel. After RNA splicing, RCBTB1 significantly affected refractive error. Risk genes for refractive error significantly enriched in biological processes related to synaptic transmission and acetylcholine. In conclusion, our analysis provides a better understanding of potential therapeutic targets and biological pathways for refractive error.