of smoking30 including more than 1.2 mill people the CUD risk locus is genome-wide significantly associated with smoking, with the CUD risk allele increasing risk for smoking initiation, younger age at smoking initiation and continuation of smoking, but it is associated with decreasing number of cigarettes per day (Supplementary Table 7). The strongest association is observed for smoking initiation with an effect size of OR=0.954 (rs11783093), which is significantly lower than the effect size observed for CUD in iPSYCH (OR=0.73 (rs56372821); P=7.964873x10−09; Z=5.767) and smaller than in deCODE (OR=0.88; P=0.061; Z=1.87). This suggests that the locus has a pleiotropic effect on the risk of both smoking and CUD in the general population, with greatest impact on CUD risk. In order to rule out that smoking behavior is not the main factor driving the association signal on chromosome 8 in the present study, we performed several additional analyses.
