Single-cell multiomics analysis reveals cell/tissue-specific associations in bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Bipolar disorder (BD) is a complex psychiatric condition with unclear cellular origins and tissue heterogeneity.
• Understanding the genetic underpinnings and cellular pathology of BD is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the cellular origin and tissue heterogeneity in bipolar disorder (BD) by integrating multiomics data.
• To identify specific cell types and brain regions implicated in the pathogenesis of BD.
• To uncover novel genetic associations and potential molecular mechanisms underlying BD.

Main Methods:

• Integration of four distinct datasets: single-cell RNA sequencing (scRNA-seq), Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), bulk RNA-seq, and genome-wide association study (GWAS) summary data.
• Utilized the single-cell disease relevance score (scDRS) algorithm for data integration.
• Analyzed cell-type specific associations with BD across different molecular data types and brain regions, including the dorsolateral prefrontal cortex (DLPFC).

Main Results:

• Glial cells, including astrocytes, microglia, and oligodendrocyte precursor cells, were identified as the primary cytopathology associated with BD.
• Microglia showed strong associations across multiple data types (TWAS, ATAC-seq, RNA-seq).
• Significant associations between BD and glial cells were observed in the dorsolateral prefrontal cortex (DLPFC), implicating specific brain regions.

Conclusions:

• Glial cells, particularly in the DLPFC, play a significant role in the pathogenesis of bipolar disorder.
• Multiomics data integration provides valuable insights into the etiology of BD, highlighting glial cell dysfunction.
• Findings pave the way for understanding potential molecular mechanisms and therapeutic targets for BD.