Identifying biological pathways enriched in the candidate genes may provide important information for our understanding of the molecular mechanism underlying nicotine addiction. We searched for enriched pathways in the NAGenes using IPA and found 97 significant enrichment pathways (PBH≤0.01) (S2 Table). The 20 most significantly enrichment pathways are shown in Table 2. Most of the pathways were related to neurotransmission system, consistent with the fact that nicotine addiction is a neuronal disease. Among them, several pathways associated with monoamine neurotransmitters stood out, e.g., dopamine receptor signaling (ranked 4th), serotonin receptor signaling (ranked 11th), glutamate receptor signaling (ranked 14th) and GABA receptor signaling(ranked 19th), all of which play important roles in signaling transduction. Moreover, two pathways, synaptic long term potentiation (PBH = 1.07×10–3) and synaptic long term depression (PBH = 8.13×10–3) were enriched in the NAGenes (S2 Table). These two pathways were critical in synaptic plasticity development and have been reported to be involved in addiction [26–27]. In addition, we also highlighted other significantly enriched pathways, i.e., cAMP-mediated signaling, calcium signaling, G-protein coupled receptor signaling, neuropathic pain signaling in dorsal horn
