Investigating a downstream gene of Gpnmb using the systems genetics method

Ye Lu, Diana Zhou, Hong Lu, Fuyi Xu, Junming Yue, Jianping Tong, Lu Lu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)222-236
Number of pages15
JournalMolecular vision
Volume25
StatePublished - Jan 1 2019

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Glycoproteins
Glaucoma
Genes
Quantitative Trait Loci
Oxidative Stress
Apoptosis
Phenotype
Gene Ontology
neuromedin B
Retinal Ganglion Cells
Gene Regulatory Networks
Optic Nerve
Computational Biology
Retina
teleocalcin
Gene Expression

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Lu, Y., Zhou, D., Lu, H., Xu, F., Yue, J., Tong, J., & Lu, L. (2019). Investigating a downstream gene of Gpnmb using the systems genetics method. Molecular vision, 25, 222-236.

Investigating a downstream gene of Gpnmb using the systems genetics method. / Lu, Ye; Zhou, Diana; Lu, Hong; Xu, Fuyi; Yue, Junming; Tong, Jianping; Lu, Lu.

In: Molecular vision, Vol. 25, 01.01.2019, p. 222-236.

Research output: Contribution to journalArticle

Lu, Y, Zhou, D, Lu, H, Xu, F, Yue, J, Tong, J & Lu, L 2019, 'Investigating a downstream gene of Gpnmb using the systems genetics method', Molecular vision, vol. 25, pp. 222-236.
Lu Y, Zhou D, Lu H, Xu F, Yue J, Tong J et al. Investigating a downstream gene of Gpnmb using the systems genetics method. Molecular vision. 2019 Jan 1;25:222-236.
Lu, Ye ; Zhou, Diana ; Lu, Hong ; Xu, Fuyi ; Yue, Junming ; Tong, Jianping ; Lu, Lu. / Investigating a downstream gene of Gpnmb using the systems genetics method. In: Molecular vision. 2019 ; Vol. 25. pp. 222-236.
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