Analyzing the genes related to nicotine addiction or schizophrenia via a pathway and network based approach

The prevalence of tobacco use in people with schizophrenia is much higher than in general population, which indicates a close relationship between nicotine addiction and schizophrenia. However, the molecular mechanism underlying the high comorbidity of tobacco smoking and schizophrenia remains largely unclear. In this study, we conducted a pathway and network analysis on the genes potentially associated with nicotine addiction or schizophrenia to reveal the functional feature of these genes and their interactions. Of the 276 genes associated with nicotine addiction and 331 genes associated with schizophrenia, 52 genes were shared. From these genes, 12 significantly enriched pathways associated with both diseases were identified. These pathways included those related to synapse function and signaling transduction, and drug addiction. Further, we constructed a nicotine addiction-specific and schizophrenia-specific sub-network, identifying 11 novel candidate genes potentially associated with the two diseases. Finally, we built a schematic molecular network for nicotine addiction and schizophrenia based on the results of pathway and network analysis, providing a systematic view to understand the relationship between these two disorders. Our results illustrated that the biological processes underlying the comorbidity of nicotine addiction and schizophrenia was complex, and was likely induced by the dysfunction of multiple molecules and pathways.