TNF and nicotine dependence: As for FREM1, aminoacyl-tRNA biosynthesis, glycosaminoglycan degradation and glycosphingolipid biosynthesis-ganglio series and selenocompound metabolism protein export were significantly enriched in the high FREM1subgroup, whereas IL-17 signaling pathway, legionellosis, malaria, nicotine addiction, TNF signaling pathway were significantly enriched in the low FREM1 subgroup (Fig. 8B).