Other notable molecular roles for the 19 causal genes in depression are magnesium homeostasis, glycosylation, neuronal apoptosis, and cell adhesion. CNNM2 plays an important role in magnesium homeostasis44, and magnesium is a key component in neuronal maturation and neuropathology via its role in cell proliferation, differentiation, survival, and neuronal network formation45. CNNM2 has also been implicated in schizophrenia and impaired brain development44,46, and our finding suggests it contributes to the pathogenesis of depression. Both B3GALTL and GMPPB implicate a role for glycosylation, a common post-translational modification. B3GALTL, as mentioned above, is a glycosyltransferase that adds glycans to proteins in glycosylation41, and GMPPB, a GDP-mannose pyrophosphorylase B, catalyzes the formation of GDP-mannose, which is required for the glycosylation of lipids and proteins47. PSMB4 is a proteasome that is responsible for protein degradation and is involved in neuronal apoptosis in neuroinflammation48. Finally, CDH13 encodes a calcium-dependent cell adhesion protein that has been implicated in major depression, bipolar disorder, schizophrenia, ADHD, and autism spectrum disorder49. Taken together, these 19 genes implicate a number of molecular pathways involved in depression, and, in particular, emphasize the role of the synapse in depression.
