Investigating causal relationships between gene expression and major depressive disorder via brain bulk-tissue and cell type-specific eQTL: A Mendelian randomization and Bayesian colocalization study

May 1, 2025Journal of affective disorders

Links between gene activity and major depression in brain cells using genetic analysis

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Abstract

Five genes—BTN3A2, SLC12A5, AREL1, GMPPB, and ZNF660—show strong causal evidence for major depressive disorder (MDD).

  • Integrative analyses linked gene expression to MDD using data from 170,756 cases and 329,443 controls.
  • Cell type-specific investigations identified additional candidate genes associated with MDD in excitatory neurons, astrocytes, and oligodendrocytes.
  • Causal gene expression profiles varied significantly between bulk-tissue and specific brain cell types.
  • Findings suggest that understanding cellular differences is crucial for precision therapeutic strategies in MDD.

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