Significant genetic influences have been reported across stages of nicotine self-administration including initiation, smoking persistence, nicotine dependence, and nicotine withdrawal. Additive genetic effects account for 30-75% of the total variance of nicotine dependence across several studies (Agrawal et al. 2008; Pergadia et al. 2006). Similarly, a meta-analysis of 17 twin studies estimated a weighted mean heritability of liability for smoking persistence of 59% in male smokers and 46% female smokers (Li et al. 2003). Few twin studies have reported measures of average lifetime cigarette use, often measured as pack-years, although this measure has been used more consistently in the structural imaging studies (Gallinat et al. 2006). Subsequently, there is a need to assess the genetic contributions of average lifetime cigarette use as an important smoking-related behavior to determine its relationship with brain structure in a twin sample.
