Based on non-significant results in the GWAS of nicotine ND discussed above (Bierut et al. 2007) and significant results in three subsequent studies of ND and/or lung cancer (Thorgeirsson et al. 2008, Amos et al. 2008; Hung et al. 2008), a cluster of nicotinic receptor genes has emerged as a candidate region for phenotypes related to cigarette smoking. These variants also appear to modulate risk for several other forms of substance dependence, including AD. Although the discovery of the effect on ND-related traits is recent and there have been only a few articles to date examining the association of variation in nicotinic receptor genes and AD and related phenotypes, the findings from these studies are unusually consistent. Variants at this cluster have been associated to risk for AD (Wang et al. 2008), early initiation of alcohol use (Schlaepfer et al. 2008), and level of response to alcohol (Joslyn et al. 2008). The mechanism by which genetic variation in these genes might affect risk for AD is not yet clear, but in view of the known shared genetic liability between ND and AD, the finding is not surprising.
