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The findings may be due to two factors: the populations growth and ageing, which have intensified smoking and increased disease burden, and global anti-smoking initiatives over recent decades, such as price and tax controls, public smoking bans, public awareness campaigns about tobacco risks, and enhanced global cooperation, as outlined in the WHO Framework Convention on Tobacco Control (FCTC) 8-11

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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

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