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- Title
Identification and replication of RNA-Seq gene network modules associated with depression severity.
- Authors
Le, Trang T.; Savitz, Jonathan; Suzuki, Hideo; Misaki, Masaya; Teague, T. Kent; White, Bill C.; Marino, Julie H.; Wiley, Graham; Gaffney, Patrick M.; Drevets, Wayne C.; McKinney, Brett A.; Bodurka, Jerzy
- Abstract
Genomic variation underlying major depressive disorder (MDD) likely involves the interaction and regulation of multiple genes in a network. Data-driven co-expression network module inference has the potential to account for variation within regulatory networks, reduce the dimensionality of RNA-Seq data, and detect significant gene-expression modules associated with depression severity. We performed an RNA-Seq gene co-expression network analysis of mRNA data obtained from the peripheral blood mononuclear cells of unmedicated MDD (n = 78) and healthy control (n = 79) subjects. Across the combined MDD and HC groups, we assigned genes into modules using hierarchical clustering with a dynamic tree cut method and projected the expression data onto a lower-dimensional module space by computing the single-sample gene set enrichment score of each module. We tested the single-sample scores of each module for association with levels of depression severity measured by the Montgomery-Åsberg Depression Scale (MADRS). Independent of MDD status, we identified 23 gene modules from the co-expression network. Two modules were significantly associated with the MADRS score after multiple comparison adjustment (adjusted p = 0.009, 0.028 at 0.05 FDR threshold), and one of these modules replicated in a previous RNA-Seq study of MDD (p = 0.03). The two MADRS-associated modules contain genes previously implicated in mood disorders and show enrichment of apoptosis and B cell receptor signaling. The genes in these modules show a correlation between network centrality and univariate association with depression, suggesting that intramodular hub genes are more likely to be related to MDD compared to other genes in a module.
- Publication
Translational Psychiatry, 2018, Vol 8, Issue 1, p1
- ISSN
2158-3188
- Publication type
Article
- DOI
10.1038/s41398-018-0234-3