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Tobacco Smoking Addiction: Epidemiology, Genetics, Mechanisms, and Treatment pp 199–213Cite as

Identification of Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

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Abstract

Twin and family studies reveal a significant genetic contribution to the risk of smoking initiation and progression (SI/P) and to ND and to the likelihood of smoking cessation (SC). Numerous genes have been implicated in these smoking-related behaviors, especially ND. However, no study has presented a comprehensive, systematic view of the genetic factors associated with these important smoking-related phenotypes. By searching the literature on these behaviors, we identified 16, 99, and 75 genes that have been associated with SI/P, ND, and SC, respectively. We then determined whether these genes were enriched in pathways important in the neuronal and brain functions underlying addiction. We identified 9, 21, and 13 pathways enriched in the genes associated with SI/P, ND, and SC, respectively. Among these pathways, four signaling pathways were common to all of the three smoking-related phenotypes: i.e., calcium, cAMP-mediated, dopamine receptor, and G-protein-coupled receptor. Further, serotonin receptor signaling and tryptophan metabolism pathways are shared by SI/P and ND; the tight junction signaling pathway is shared by SI/P and SC; and gap junction, neurotrophin/TRK signaling, synaptic long-term potentiation, and tyrosine metabolism are shared by ND and SC. Together, these findings demonstrate significant genetic overlap for these three related phenotypes. Although identification of susceptibility genes for smoking-related behaviors is still in an early stage, the approach utilized in this chapter has the potential to overcome the hurdles caused by factors such as genetic heterogeneity and small samples and thus should yield greater insights into the genetic mechanisms underlying these complex phenotypes.

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Acknowledgment

This chapter was modified from the paper published by our group in Neuropsychopharmacology (Wang and Li 2010). The related contents are reused with permission.

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Authors and Affiliations

  1. University of Virginia, Charlottesville, USA

    Ming D. Li

  2. Zhejiang University, Hangzhou, China

    Ming D. Li

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Li, M.D. (2018). Identification of Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation. In: Tobacco Smoking Addiction: Epidemiology, Genetics, Mechanisms, and Treatment. Springer, Singapore. https://doi.org/10.1007/978-981-10-7530-8_12

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