rs2273500 was presented in one of our prior reports as having a suggestive, but nonsignificant, association with nicotine dependence (N=1929, P=0.081).82 By using the multidimensional FTND measure of physiological dependence paired with 1000 Genomes imputation in a large sample, the current study provides the first genome-wide level of significant evidence supporting specific CHRNA4 variant associations with nicotine dependence, which were not observed in prior studies of CPD with larger sample sizes. This evidence concerns the gene CHRNA4 and nicotine dependence.