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However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, using the summary data from genome wide association studies of smoking phenotypes (<jats:italic>N<\/jats:italic>\u2009=\u2009323,386\u2013805,431), schizophrenia (<jats:italic>Ncases<\/jats:italic>\u2009=\u200953,386, <jats:italic>Ncontrols<\/jats:italic>\u2009=\u200977,258), and antisocial behavior (<jats:italic>N<\/jats:italic>\u2009=\u200985,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two\u2010step MR approach, we further examined whether causal effects of smoking phenotypes\/schizophrenia on antisocial behavior were mediated by schizophrenia\/smoking phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR\u2009=\u20092.06, 95% CI\u2009=\u20091.77\u20132.39, <jats:italic>p<\/jats:italic>\u2009=\u20094.36\u2009\u00d7\u200910<jats:sup>\u221221<\/jats:sup>; AgeSmk: OR\u2009=\u20090.32, 95% CI\u2009=\u20090.16\u20130.62, <jats:italic>p<\/jats:italic>\u2009=\u20098.11\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>, 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\u2009=\u20091.28, 95% CI\u2009=\u20091.17\u20131.41, <jats:italic>p<\/jats:italic>\u2009=\u20092.53\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>; CigDay: OR\u2009=\u20091.16, 95% CI\u2009=\u20091.06\u20131.27, <jats:italic>p<\/jats:italic>\u2009=\u20091.60\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>, Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion\u2009=\u20096.92%, 95% CI\u2009=\u20090.004\u20130.03, <jats:italic>p<\/jats:italic>\u2009=\u20099.66\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14430","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T08:09:26Z","timestamp":1693469366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Schizophrenia mediating the effect of smoking phenotypes on antisocial behavior: A Mendelian randomization analysis"],"prefix":"10.1111","volume":"30","author":[{"given":"Minghui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ultrasound Tianjin Medical University General Hospital Airport Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Tianjin Key Laboratory of Functional Imaging Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer  Tianjin 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