The strongest genetic contribution to nicotine dependence comes from variation in the nicotinic receptor subunits, and the most compelling genetic evidence is provided by several large-scale GWAS meta-analyses of smoking behavior (Liu et al., 2010; Thorgeirsson et al., 2010; Tobacco and Genetics Consortium, 2010). Because smoking is a major contributor to many illnesses, cigarettes smoked per day (CPD), a proxy phenotype for nicotine dependence, has been measured in many genetic studies, and this has allowed meta-analyses of over 80,000 individuals of European ancestry. These genetic meta-analyses of cigarettes smoked per day confirm that two chromosomal regions containing nicotinic receptor subunit gene clusters influence smoking behavior.
