To extend our GWAS findings and gain insight into the potential behavioral basis for the association of PCDH-α, -β and -γ gene SNPs with NicW, we investigated one of the genome-wide significant SNPs, rs31746, in relation to withdrawal characteristics in a sample of current smokers who participated in an IV nicotine infusion laboratory study (n=179). Because this SNP was directly genotyped by all GWAS arrays, we considered it the strongest association signal and the best SNP in the region to select for follow-up analysis. The laboratory procedure was initiated after the subjects completed an overnight (~10 h) period of smoking abstinence. This time period is sufficient for the development of withdrawal symptoms in dependent smokers.54, 55 Following the IV nicotine infusion session, features of NicW were lower than at the pre-infusion baseline (main effect of time point: BQSU:F(1,175)= 105.89, P < 0.001; MNWS: F(1,177)=63.01, P < 0.001). The change in BQSU, but not MNWS, in response to the nicotine infusion session differed by rs31746 genotype (genotype by time point interaction: BQSU: F(1,175)= 5.37, P = 0.022) (Figure 3A). There was
