DOI: 10.1101/497784Dec 17, 2018Paper

Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

BioRxiv : the Preprint Server for Biology
Catharine E. KrebsRoel A Ophoff

Abstract

Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. We performed a whole blood transcriptome analysis in a BD case-control sample (Nsubjects = 480) by RNA sequencing. 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. Our findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but underline the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic stud...Continue Reading

Related Concepts

Bipolar Disorder
Mental Depression
Pharmaceutical Preparations
Gene Expression
Genes
Lithium
Neutrophil
Schizophrenia
Venous Blood Sampling
Widespread

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