Genetic Basis of Tobacco Use Disorder

Tobacco use disorder (TUD) is a complex multifactorial condition resulting from the interplay between nicotine-induced neurobiological adaptations, behavioral and learning processes, environmental influences, and individual genetic susceptibility. Genetic research has progressively evolved from twin and family studies through candidate-gene approaches to large-scale genome-wide association studies (GWAS), substantially improving our understanding of the genetic architecture of tobacco use and nicotine dependence. This review summarizes the current evidence on the genetic basis of TUD, with particular emphasis on major biological pathways. We also discuss the limitations of early candidate-gene studies and the paradigm shift introduced by large GWAS and meta-analyses, and polygenic risk scores, which indicate that tobacco use and nicotine dependence have a highly polygenic and pleiotropic architecture. Finally, we review the potential clinical applications of genetic information in smoking-cessation treatment, while highlighting current limitations in clinical translation. In the future, it is clear that a multidisciplinary approach-combining genetics, clinical practice, and social sciences-will be necessary to transform tobacco use management into a precision-based model and reduce its impact on public health.