Causal effects of lifetime smoking on risk for depression and schizophrenia: Evidence from a Mendelian randomisation study

Smoking prevalence is higher amongst individuals with schizophrenia and depression, compared to the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). We conducted a GWAS of lifetime smoking behaviour (capturing smoking duration, heaviness and cessation) in a sample of 463,003 individuals from the UK Biobank, and validated the findings via MR analyses of positive control outcomes (e.g., lung cancer). Further MR analyses provided evidence that smoking is a causal risk factor for both schizophrenia and depression. We also found some evidence that genetic liability for both depression and schizophrenia cause increased lifetime smoking. These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking. The genetic variants we identify for lifetime smoking have the potential to be used in further MR studies.