We conducted a 1000 Genomes–imputed GWAS meta-analysis of nicotine dependence across five study samples (total N=17 074), identified the alpha-4 nicotinic receptor subunit (CHRNA4) gene as a novel genome-wide significant locus, tested top CHRNA4 variants for replication in five independent study samples (total N=7469) and conducted follow-up association testing with lung cancer using six study samples (total N=12 160 cases and 16 838 controls). This evidence concerns the gene CHRNA4 and lung cancer.