Based on the GWAS findings, we investigated the association of an identified NicW risk allele in the protocadherin (PCDH)-α, -β and -γ gene cluster with characteristics of NicW in an independent intravenous (IV) nicotine infusion study. The IV nicotine infusion study included tobacco smokers who had completed a ~10 hour period of smoking abstinence. We also characterized the effects of the NicW-associated risk allele on gene regulatory mechanisms and PCDH-α, -β and -γ gene expression using publically available transcriptomic and epigenomic data from postmortem human brain.