Multiple large-scale, independent association studies conclusively demonstrate that variants in the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic receptor subunit genes on chromosome 15q25.1 are associated with nicotine dependence, smoking behavior, lung cancer, and chronic obstructive pulmonary disease in European-Americans (Amos et al., 2008, Berrettini et al., 2008, Bierut et al., 2008, Broderick et al., 2009, Caporaso et al., 2009, Chen et al., 2009, Freathy et al., 2009, Grucza et al., 2008, Hung et al., 2008, Le Marchand et al., 2008, Lips et al., 2009, Liu et al., 2008, Pillai et al., 2009, Saccone et al., 2007, Sherva et al., 2008, Spitz et al., 2008, Stevens et al., 2008, Thorgeirsson et al., 2008, Wang et al., 2009, Weiss et al., 2008, Young et al., 2008). Recent work reveals that some of these variants also affect nicotine dependence and lung cancer risk in African-Americans (Li et al., 2010, Saccone et al., 2009b, Schwartz et al., 2009) and in Asians (Shiraishi et al., 2009, Wu et al., 2009). These strong, consistent findings in CHRNA5-CHRNA3-CHRNB4 raise the question of whether additional cholinergic nicotinic receptor subunit (CHRN) genes also play an important role in risk for these diseases.
