Fifth, there is a high degree of zero inflation in the distribution of our lifetime smoking index scores with 54% of the sample being never smokers and therefore receiving a score of zero. We decided not to transform the variable given the desire to have interpretable effect sizes for MR and we decided not to exclude never smokers because our instrument is designed to be used in two-sample MR without the need to stratify into smokers and non-smokers. Despite the zero inflation, we see similar effects for lifetime smoking and smoking initiation suggesting that this has not impaired the score. Sixth, the lifetime smoking score was simulated using all-cause mortality and lung cancer as outcomes. The pattern of association between smoking and lung cancer risk compared with risk for schizophrenia and depression is likely to be different. However, increased mortality amongst individuals with schizophrenia and depression is in large part due to smoking-related mortality (Royal College of Physicians, 2013). The effects were modelled on all-cause mortality and lung cancer but no difference to the best fitting value of half-life was
