The gene CHRNA4, which encodes the nicotinic acetylcholine receptor α4 subunit, is a candidate gene for ND risk. The gene maps to 20q13.3 and contains 6 exons spanning ~17kb of genomic DNA. CHRNA4 is highly expressed in the central nervous system, and its protein product is part of high affinity receptors (α4β2) for nicotine. It plays a major role in tolerance, reward, and the modulation of mesolimbic dopamine function, all of which are critical to the development of ND (Tapper et al., 2004). Although some genetic association studies support the role of CHRNA4 in smoking-related behaviors (Feng et al., 2004; Li et al., 2005; Hutchison et al., 2007; Breitling et al., 2009), there have been conflicting results (Ehringer et al., 2007; Weiss et al., 2008; Etter et al., 2009). GWAS studies on smoking behavior have not indentified CHRNA4 gene as a risk locus (Berrettini et al., 2008; Thorgeirsson et al., 2008; Caporaso et al., 2009; Liu et al., 2009; Vink et al., 2009; Tobacco and Genetics Consortium 2010; Liu et al., 2010; Thorgeirsson 2010). Our meta-analysis of linkage scans of
