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Network-based integrative analysis of lithium response in bipolar disorder using transcriptomic and GWAS data

ABSTRACT: Lithium is the gold standard treatment for bipolar disorder. The goal of this study was to identify gene expression networks associated with lithium response. RNAseq data was obtained from IPSC derived neurons from lithium responders and non-responders. Focal adhesion was the network most associated with response.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205422 | GEO | 2022/06/09

REPOSITORIES: GEO

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MicroRNA expression data from lymphoblastoid cell lines from patients with bipolar disorder

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Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

Project description:BACKGROUND: Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use. METHODS: We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk. RESULTS: While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD. CONCLUSIONS: These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.

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Network-based integrative analysis of lithium response in bipolar disorder using transcriptomic and GWAS data

Project description:Network-based integrative analysis of lithium response in bipolar disorder using transcriptomic and GWAS data

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Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

Project description:Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

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A Pharmcogenetic Study of Bipolar Disorder in a Taiwanese Han Chinese Population (TWBP)

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Signaling Mechanisms in Initiation of Lithium-Induced Nephrogenic Diabetes Insipidus

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