First time sensations plausibly affect the probability of smoking a whole cigarette; in line with this, in our study sample positive and negative first time sensations are associated with earlier and later age of initiation, respectively. In order to evaluate whether the association on 19q13.33 was independent of first time sensations, we included them as covariates in the follow‐up analysis, and detected genome‐wide significant association. Further, mediation analysis confirmed that the effect of the top SNP, rs73050610, is independent of first time sensations, and thus the effect is likely due to other mechanisms besides the initial sensations experienced after the first‐ever dose of nicotine. The functional annotation with GWAVA suggests that rs3843746, which is in complete LD with rs73050610 in the Finnish population (D′ = 1.00, r 2 = 0.979), is a CTCF‐binding region variant. CTCF is involved in multiple regulatory influences on expression of genes, suggesting that the highlighted SNP may have a role in regulating nearby genes. Both of the flanking genes have functions relevant for smoking behavior. TRPM4 is a calcium‐activated ion channel involved in many activities
