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Results: Genetically predicted higher level of smoking initiation was significantly associated with reduced clozapine ( = 0.14, P = 4.53E-04) concentrations and norclozapine concentrations ( = 0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations ( = 0.42, P = 1.70E-14), norclozapine concentrations ( = 0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine ( = 0.15, P = 5.35E-07), survived after the Bonferroni correction ( P = 0.05/6 = 0.008)