Schizophrenia mediating the effect of smoking phenotypes on antisocial behavior: A Mendelian randomization analysis
Minghui Zhang, Jie Tang, Wei Li, Kaizhong Xue, Zirui Wang, Yayuan Chen, Qiang Xu, Dan Zhu, Mengjing Cai, Juanwei Ma, Jia Yao, Yijing Zhang, He Wang, Feng Liu, Lining Guo- Pharmacology (medical)
- Physiology (medical)
- Psychiatry and Mental health
- Pharmacology
Abstract
Aims
Previous studies have indicated that smoking is linked to an increased risk of developing schizophrenia, and that individuals with schizophrenia are more prone to engaging in antisocial behavior. However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear.
Methods
In the present study, using the summary data from genome wide association studies of smoking phenotypes (N = 323,386–805,431), schizophrenia (Ncases = 53,386, Ncontrols = 77,258), and antisocial behavior (N = 85,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two‐step MR approach, we further examined whether causal effects of smoking phenotypes/schizophrenia on antisocial behavior were mediated by schizophrenia/smoking phenotypes.
Results
The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR = 2.06, 95% CI = 1.77–2.39, p = 4.36 × 10−21; AgeSmk: OR = 0.32, 95% CI = 0.16–0.62, p = 8.11 × 10−4, Bonferroni corrected). However, there was no causal effect that liability to schizophrenia leads to smoking phenotypes. MR evidence also revealed causal influences of SmkInit and the amount smoked (CigDay) on antisocial behavior (SmkInit: OR = 1.28, 95% CI = 1.17–1.41, p = 2.53 × 10−7; CigDay: OR = 1.16, 95% CI = 1.06–1.27, p = 1.60 × 10−3, Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion = 6.92%, 95% CI = 0.004–0.03, p = 9.66 × 10−3).
Conclusions
These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior.