Genetic influences on smoking: a brief review.

Smoking is a complex behavior influenced by environ-mental and genetic factors. A number of twin studies demonstrate genetic influences on multiple aspects of smoking including initiation, dependence, continuation, amount consumed, and cessation. It is likely that this genetic risk involves a complex interaction between multiple genes in different biologic pathways. These may include genes involved in the general aspect of dependence (eg, genes within the dopaminergic system) and those more specific to nicotine dependence (eg, genes encoding nicotinic acetylcholine receptors and nicotine-metabolizing enzymes). Genome-wide linkage analyses and gene association studies provide approaches for identifying these genes. This review provides a brief highlight of data from some of the candidate gene association studies and discusses some of the discrepancies found in the literature. In addition, the authors have reviewed some recent studies examining how genetic variations in drug-metabolizing enzymes and drug targets can influence the response to treatment with drugs such as bupropion and nicotine.These latter studies provide the potential for maximizing treatment efficacy by individualizing the type, dosage, and duration of the treatment based on an individual's genotype/phenotype. Significant advances have been made in understanding the genetic contribution to smoking behaviors. These and future studies will provide potential directions for novel prevention and treatment strategies.