Analysis Supports Netrin 1 Receptor Gene as Depression Risk Gene
Genome wide association studies (GWAS) for psychiatric disorders such as depression have been extensively conducted, and more recently, transcriptome-wide analyses in the tissues of brain regions relevant to the pathogenesis of depression have been performed. The integration of multi-omic data has been used to unveil risk genes associated with depression, and these genes could be the next generation of anti-depressant targets.
A recent study used data-based Mendelian randomization (SMR) and integrative risk gene selector approaches to integrate multi-omics data to prioritise high-confidence risk genes for depression followed by independent replication across distinct populations. The analyses identify multiple high-confidence risk-genes and supported a pivotal role of the netrin 1 receptor gene (DCC) across different populations. The netrin 1 receptor gene codes for a transmembrane protein that is a cell adhesion molecule that mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand, and has been associated with depression previously.
They performed some more analysis which suggested that DCC significantly predicts neuroticism, cognitive function, putamen structure in general populations.
They also studied the gene expression correlation and the pathway analysis in the dorsolateral prefrontal cortex (DLPFC) showed that DCC could participate in the biological processes that underlie synaptic plasticity, axon guidance, circadian entrainment as well as learning and long-term potentiation.
The study concluded that the results support the recent findings that the DCC gene is an important susceptibility gene for depression and could be a potential target for antidepressants.