Additionally, the transcript expression of the genes in this region was nominally regulated by some nicotine dependence-related genes, including ITGA4, KCNN3, CCBE1, SGCZ, PARK2, PBK and CTNNA3. All of these genes have ever been associated with nicotine dependence or related traits before[Bierut et al., 2007; Uhl et al., 2010; Uhl et al., 2008], although some of them have not been well replicated yet. ITGA4 and KCNN3 regulated all four genes in SH3BP5-NR2C2 region in brain, and CCBE1 and SGCZ regulated these four genes in PBMC. PARK2 and PBK regulated SH3BP5 in PBMC and brain, respectively; and CTNNA3 regulated CAPN7 in brain. Although these regulatory effects were not significant after correction for multiple testing, those effects replicable across four genes might be robust. Biological functions of these nicotine dependence-related genes together with NR2C2, ZFYVE20, CAPN7 and SH3BP5 were summarized in Table S5. Most of these genes are integrin- or calcium-related, or encode proteases (Table S5), suggesting other possible molecular mechanisms that might be implicated in alcohol and nicotine dependence.
