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A randomized controlled trial study is the best method for verifying causality, but it is lengthy, expensive, and fraught with problems, so a successful approach is to use genetic variants as exposure indicators that are not subject to the influences that compromise conventional study designs, an approach known as Mendelian randomization (MR) ( Herein, we employed the two-sample MR method to assess the effect of smoking, coffee drinking, or alcohol consumption on clozapine metabolism in order to determine if substance use in typically ingested quantities effects clozapine concentrations in individuals with schizophrenia