Cigarette use is a leading risk factor for multiple illnesses and a major public health concern.1 Twin and family studies have demonstrated that smoking is influenced both by genetic and environmental factors.2, 3 Genome-wide association studies (GWAS) in populations of European ancestry have identified common genetic variation associated with smoking behaviors. An initial GWAS of smoking quantity identified associations with genetic variants in several of the nicotinic acetylcholine receptors clustered on chromosome 15.4 Meta-analyses in three large consortia of smoking behaviors confirmed the GWAS finding and refined the association signal within the locus.5, 6 Additional genetic risk variants have been identified for smoking quantity, including neuronal nicotinic acetylcholine receptor subunit beta-3 (CHRNB3) and alpha-6 (CHRNA6),4 cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6)4, 6 and LOC10018894,6 a variant residing in a gene whose function is currently unknown. Of the variants identified to date, each genetic variant, or single-nucleotide polymorphism (SNP), accounts for a very small proportion of the variance in smoking behavior (<2%). Smoking behaviors are complex genetic traits, influenced by multiple genetic variants,7, 8 which likely interact with
