Functional features, biological pathways, and protein interaction networks of addiction-related genes.

Addictions are chronic and common brain disorders affected by many genetic, environmental, and behavioral factors. Recent genome-wide linkage and association studies have revealed several promising genomic regions and multiple genes relating to addictions. To explore the underlying biological processes in the development of addictions, we used 62 genes recently reviewed by Li and Burmeister (2009) as representative addiction-related genes, and then we investigated their features in gene function, pathways, and protein interaction networks. We performed enrichment tests of their Gene Ontology (GO) annotations and of their pathways in the Ingenuity Pathways Analysis (IPA) system. The tests revealed that these addiction-related genes were highly enriched in neurodevelopment-related processes. Interestingly, we found circadian rhythm signaling in one of the enriched pathways. Moreover, these addiction-related genes tended to have higher connectivity and shorter characteristic shortest-path distances compared to control genes in the protein-protein interaction (PPI) network. This investigation is the first of such kind in addiction studies, and it is useful for further addiction candidate-gene prioritization and verification, thus helping us to better understand molecular mechanisms of addictions.