II) Furthermore, we evaluated by elementary simulation analysis how likely it would be to observe an odds ratio of 0.728 if the signal was primarily driven by tobacco smoking, by assuming a true odds ratio of smoking = 0.95430. We assigned plausible values for the prevelance of tobacco smoking among minor and major allele carriers of rs5637282 as well as CUD among tobacco users and non-users, and empirically approximated the probability of observing an odds ratio of 0.728. The largest P-value encountered was 8.69x10−3 (212 scenarios were tested), supporting that it is very unlikely that the OR we observe for CUD could be caused by tobacco smoking alone (Methods and Supplementary Table 9).
