were investigated to test the causal links between traits related to tobacco smoking with psychiatric disorders and behavioural traits. Smoking initiation is affected by educational attainment but not by cognitive ability, suggesting a contribution to health inequality in less-educated people110. Among personality traits, genetic liabilities to neuroticism and extraversion have a causal effect with smoking severity and initiation, respectively111. Studies investigating causality between smoking behaviours and schizophrenia showed conflicting results112, 113, whereas depression and bipolar disorder appear to have a bidirectional relationship with lifetime smoking and smoking initiation112, 114. For physical health, several novel causal effects were observed such as smoking initiation on stroke risk115 and fracture risk116 or body mass index on being a smoker117. Evidence of bidirectional associations was observed between cannabis use and schizophrenia34, 118, 119. Conversely, ADHD showed a causal effect on cannabis initiation together with smoking initiation and severity77, 120. With respect to alcohol-drinking behaviours, both major depression and ADHD have causal effects on AUD risk but not on alcohol consumption82, 120. Although these studies provided novel insights useful to understand the mechanisms underlying comorbidities of SUDs, MR analyses present several limitations that should be considered carefully when interpreting their findings in the context of
