Our initial association finding emerged from a GWAS of six separately analyzed samples derived from three independent cohorts containing nearly 4,400 EA subjects and more than 3,600 AA subjects. The results of the nicotine infusion laboratory study, which used a different study design from the GWAS, supported the GWAS finding by showing an association of the rs31746*A allele with a greater change in the urge to smoke, a clinically important characteristic of NicW. This critical insight suggests one potential mechanism, regulation of smoking urges and craving, by which rs31746 might influence NicW risk. However, the laboratory study subjects had a ~10 hour period of smoking abstinence and there was no association of rs31746 to NicW characteristics at the smoking abstinence baseline prior to nicotine infusion. Evaluating genotype effects in subjects after a longer period of abstinence might also be informative given prior work suggesting that some withdrawal symptoms peak 2–3 days post-cessation57. The limited abstinence period may be why we observed effects for QSU but not MNWS. Although withdrawal symptoms and urges are similar, and often correlated, constructs, they follow
