The top ten pathways of the 37 pathways enriched in downregulated DEGs were glutamatergic synapse, circadian entrainment, GABAergic synapse, retrograde endocannabinoid signaling, calcium signaling pathway, dopaminergic synapse, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes, insulin secretion and nicotine addiction (Additional file 17: Figure S8 and Additional file 14: Table S8). The gene discussed is INS; the disease is nicotine dependence.