Both human and animal research support an a priori hypothesis that age of onset of daily smoking may influence the association of genetic risk variants with measures of nicotine dependence. In humans, early onset of smoking is associated with greater consumption of cigarettes in adulthood [10]–[15], a relative inability to quit smoking [10], [16]–[18], and a more severe form of nicotine dependence [13], [19]–[22]. Research in rodents shows that nicotine exposure during periadolescence induces long-lasting biochemical, anatomical, physiological, and behavioral changes that differ markedly from those seen with adult exposure [23]–[27].
