This article is more than 5 years old. Information may no longer be current.

RNA sequencing identifies new genes associated with bipolar disorder

RNA sequencing of postmortem brain samples from patients with bipolar disorder identified dysregulation of G-protein coupled receptors, novel bipolar disorder genes and noncoding transcriptome.

“In order to understand the role that coding and noncoding RNAs play in brain regulation and how their potential dysregulation could affect brain function and ultimately onset of bipolar disorder, we investigated gene expression changes in postmortem brain tissue from bipolar disorder cases using RNA sequencing,” Cristiana Cruceanu, BSc, of McGill University, Montreal, and colleagues wrote. “While the precise bipolar disorder neuroanatomical circuits are not exactly known and there are data supporting the involvement of diverse brain regions, there is strong support for the role of the anterior cingulate cortex in the regulation of ideo-affective and mood functions and thus in the neurobiology of bipolar disorder.”

Researchers used RNA sequencing in postmortem tissue from the anterior cingulate cortex of 13 patients with bipolar disorder and 13 matched comparison patients. They computed differential expression, detecting a global pattern of downregulation with 10 significant transcripts at a false discovery rate of 5% or less. All 10 genes were replicated in an independent RNA sequencing data set from the anterior cingulate cortex (n = 61).

Genes coding for class A of the G protein-coupled receptor family of genes, including somatostatin receptor 2 (SSTR2), cholingeric receptor, muscarinic 2 (CHRM2), and relaxin/insulin-like family peptide receptor 1 (RXFP1), were significant.

Gene ontology analysis of the differentially expressed genes indicated an overrepresentation of genes involved in G protein-coupled receptor regulation.

Researchers followed up on the top genes by querying the effect of treatment with mood stabilizers commonly prescribed for bipolar disorder, and found that they modulated gene expression.

“This analysis is of interest because more and more reports have emerged in the last few years documenting the importance of noncoding RNAs in normal brain development, maintenance, and aging, as well as a variety of conditions including neurodevelopmental disorders such as autism,” the researchers wrote. “Though they did not pass multiple testing corrections, the top three (ranked by P value) most significant lincRNAs were significantly downregulated when validated using quantitative real-time PCR, suggesting that these lincRNAs should be further investigated in bipolar disorder.” – by Amanda Oldt

Disclosure: Cruceanu reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.