Among these, the TGF-beta signaling pathway, T cell receptor signaling pathway, and Nicotine addiction pathway were highly enriched (p < 0.01) enriched involving relevant genes (PITX2, ID4, BMP4, DLG1, IKBKB, ICOS, GRIA3, and SLC17A6) (Figure 6b and Supplementary Table S11). This evidence concerns the gene ICOS and nicotine dependence.