We discuss briefly additional novel candidate genes mapped to regions discovered by the GSMA. In particular, we focus on the region of chromosome 17q24.3–q25.3 (bin 17.4), since this region ranks highest in the meta-analysis of the combined smoking behavior, and was consistently nominated by the meta-analysis of FTND and MaxCigs24. According to NCBI database information (http://www.ncbi.nlm.nih.gov/), there are 253 genes in 17q24.3–q25.3, among which we find two particularly promising candidate genes for smoking. One gene is G protein pathway suppressor 1 (GPS1), which suppresses G-protein and mitogen-activated signal transduction. Variants of this gene might influence the regulation of the dopamine signaling pathway and associated with smoking behavior. Another promising candidate gene is suppressor of cytokine signaling 3 (SOCS3). A recent GWAS discovered a genomewide significant association of IL15 with smoking behavior in males (50). As IL15 is an important cytokine that regulates T and natural killer cell activation and proliferation, the genetic association of IL15 with smoking may serve as paradigmatic for a novel mechanism for nicotine dependence involving immune modulation through the IL15 pathway. Hence, it is reasonable to suspect that variants in SOCS3 gene might influence the regulation of immune system through a cytokine signaling pathway.
