Considerable biochemical and pharmacological research indicates multiple genes and biochemical pathways are modulated by nicotine, leading to changes in downstream actions, neural circuit plasticity and the development of addiction. Further, twin and family studies reveal that nicotine dependence (ND) is highly heritable, with an average heritability of 0.56 for male and female smokers (Li et al. 2003a; Sullivan and Kendler 1999). A common approach for identifying vulnerability genes for ND is to conduct a linkage study followed by candidate gene-based association analysis. Susceptibility loci for ND have been reported in more than 20 linkage studies (for a recent review, see Li 2008). One of these chromosomal regions, 11p15, is where amyloid precursor protein-binding protein, family B, member 1 (APBB1) is located, which has been linked to ND in three independent samples: the Framingham Heart Study (FHS), Mid-South Tobacco Family (MSTF) samples, and Family Study for Panic Disorder (Gelernter et al. 2004; Li et al. 2003b; Wang et al. 2005).
