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Schizophrenia and Lung Cancer: Evidence from Mendelian Randomization and Genetic Pleiotropy Analysis
Zongyuan Li1,2, Wenying Xu1, Cheng Yu1
1Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Sichuan, China.
Psychiatry and Clinical Psychopharmacology
|January 21, 2026
Summary
Schizophrenia (SCZ) causally increases lung cancer (LUCA) risk, with smoking and alcohol mediating this effect. Interventions targeting these factors may reduce LUCA risk in SCZ patients.
Area of Science:
- Psychiatry and Oncology
- Genetic Epidemiology
Background:
- Observational studies on schizophrenia (SCZ) and lung cancer (LUCA) have yielded inconsistent results.
- The causal link between SCZ and LUCA remains unclear, necessitating further investigation.
Purpose of the Study:
- To investigate the potential causal effect of schizophrenia on lung cancer risk using Mendelian randomization.
Main Methods:
- Utilized genome-wide association study data for SCZ, LUCA, smoking, and alcohol consumption.
- Performed univariable and multivariable Mendelian randomization analyses.
- Employed mediation analysis to assess the role of smoking and alcohol in the SCZ-LUCA relationship.
Main Results:
- Genetically predicted SCZ was found to causally increase the risk of LUCA (OR=1.068).
- Lifetime smoking and weekly alcohol consumption partially mediated the effect of SCZ on LUCA risk.
- Sensitivity analyses confirmed the robustness of these findings.
Conclusions:
- This study provides genetic evidence for a causal relationship between SCZ and increased LUCA risk.
- Population-level interventions focused on smoking cessation and reduced alcohol consumption could mitigate LUCA risk in individuals with SCZ.
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