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

Summary

This Mendelian randomisation study used genetic variants as instrumental variables to investigate whether smoking causally influences risk for schizophrenia and depression, addressing the higher prevalence of smoking in these populations. The analysis found strong evidence that smoking increases risk for both schizophrenia (OR 2.27) and depression (OR 1.99), with consistent results across lifetime smoking and smoking initiation measures. Reverse causality analyses suggested genetic liability to depression may modestly increase smoking behaviour, but evidence for schizophrenia was mixed, indicating that the smoking–psychiatric condition associations are primarily driven by a causal effect of smoking on mental health.

UK applicability

The study used UK Biobank data and genetic instruments validated in UK populations, making findings directly applicable to understanding smoking-related psychiatric risk in the United Kingdom. The findings support public health messaging and clinical guidance in the UK regarding smoking cessation as part of mental health intervention strategies.

Key measures

Odds ratios with 95% confidence intervals for smoking effects on schizophrenia and depression; standardised beta coefficients for reverse causality (genetic liability to psychiatric conditions on smoking behaviour); GWAS data from 462,690 UK Biobank participants and PGC consortium psychiatric GWAS

Outcomes reported

The study examined bidirectional causal relationships between smoking behaviour and risk of schizophrenia and depression using genetic variants as instrumental variables. It measured odds ratios for smoking as a risk factor for each psychiatric condition and estimated effects of genetic liability to psychiatric conditions on smoking initiation and lifetime smoking behaviour.

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