Integrated Comparison of GWAS, Transcriptome, and Proteomics Studies Highlights Similarities in the Biological Basis of Animal and Human Myopia.

摘要: Purpose To identify commonalities between the genes in close proximity to genome-wide association study (GWAS) refractive error and axial length loci, proteins differentially expressed animal models of optically induced error. Methods The GWAS catalog was searched for loci significantly (P ≤ 5*10-8) associated with or length. PubMed exploratory transcriptome proteomics studies A total 15 GWAS, 7 transcriptome, 9 met inclusion criteria. Ensembl's BioMart used human orthologs from studies. These were then compared protein-coding within 1 megabase (Mb), 500 kilobases (kb), 250 kb by using GeneOverlap R package, Benjamini-Hochberg-adjusted P values odds ratios (ORs) calculated each intersection. Results near overlapped downregulated during early myopia induction animals (1Mb: OR = 1.56, 0.025; kb: 1.92, 0.010; 2.33, 0.010). There also significant overlap late (OR 4.12, 0.018). When results segregated methodologic parameters, candidate at 1.50, 0.010) but not 1.04, 0.684) time-points. Gene protein expression responses appeared well conserved across model species, there no evidence greater GWAS-transcriptome concordance similar species humans (e.g., primates mammals). Conclusions findings suggest that genetic environmental factors control ocular growth via biological pathways support continued use investigating mechanisms underlying development.