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Investigating a downstream gene of Gpnmb using the systems genetics method

PURPOSE: Glaucoma is characterized by optic nerve damage and retinal ganglion cell loss. The glycoprotein neuromedin B-associated (Gpnmb) gene is well-known to be involved in the glaucoma disease process. The purpose of this study is to identify a downstream gene through which Gpnmb affects the glau...

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Detalles Bibliográficos
Autores principales: Lu, Ye, Zhou, Diana, Lu, Hong, Xu, Fuyi, Yue, Junming, Tong, Jianping, Lu, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478243/
https://www.ncbi.nlm.nih.gov/pubmed/31057322
Descripción
Sumario:PURPOSE: Glaucoma is characterized by optic nerve damage and retinal ganglion cell loss. The glycoprotein neuromedin B-associated (Gpnmb) gene is well-known to be involved in the glaucoma disease process. The purpose of this study is to identify a downstream gene through which Gpnmb affects the glaucoma phenotypes using a systems genetics approach. METHODS: Retinal gene expression data for the BXD recombinant inbred (RI) strains (n=75) have previously been generated in our laboratory for a glaucoma study, and these data were used for genetic and bioinformatics analysis. Expression quantitative trait locus (eQTL) mapping and genetic correlation methods were used to identify a gene downstream of Gpnmb. Gene-set enrichment analysis was used to evaluate gene function and to construct coexpression networks. RESULTS: The level of Gpnmb expression is associated with a highly statistically significant cis-eQTL. Stanniocalcin 1 (Stc1) has a significant trans-eQTL mapping to the Gpnmb locus. The expression of Gpnmb and Stc1 is highly correlated in the retina and other tissues, as well as with glaucoma-related phenotypes. Gene Ontology and pathway analysis showed that Stc1 and its covariates are highly associated with apoptosis, oxidative stress, and mitochondrial activity. A generated gene network indicated that Gpnmb and Stc1 are directly connected to and interact with other genes with similar biologic functions. CONCLUSIONS: These results suggest that Stc1 may be a downstream candidate of Gpnmb, and that both genes interact with other genes in a network to develop glaucoma pathogenesis through mechanisms such as apoptosis and oxidative stress.