Mendelian randomization and single-cell expression analyses identify the causal relationship between depression and...

Area of Science:

• Genetics
• Immunology
• Psychiatry

Background:

• The causal link between chronic rhinosinusitis (CRS) and depression is not well understood.
• Investigating this relationship is crucial for understanding comorbid conditions.

Purpose of the Study:

• To determine the causal relationship between chronic rhinosinusitis and depression.
• To explore the underlying biological mechanisms using single-cell analysis.

Main Methods:

• Utilized Mendelian randomization (MR) with genome-wide association study data for CRS and depression.
• Performed bidirectional MR analysis with sensitivity testing.
• Integrated single-cell RNA sequencing data to analyze cell-type specific gene expression and interactions.

Main Results:

• Bidirectional MR analysis confirmed a causal link between CRS and depression in both directions.
• Forward MR showed depression as a risk factor for CRS (OR = 1.425, P < 0.001).
• Reverse MR indicated CRS as a risk factor for depression (OR = 1.012, P = 0.038).
• Single-cell analysis revealed altered cell-cell interactions in CRS, with myeloid cells showing a specific receptor-ligand pair.
• Identified TCF4 and MEF2C as potentially key genes in CRS-associated depression.

Conclusions:

• Established a bidirectional causal relationship between chronic rhinosinusitis and depression.
• Provides a novel perspective on the complex interplay between sinonasal inflammation and mental health.
• Highlights potential therapeutic targets for comorbid CRS and depression.