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We compared the polygenic contribution to smoking in schizophrenic patients and controls to assess if genetic factors may explain the different prevalence. Polygenic risk scores (PRSs) for smoking initiation and four genetically correlated traits were calculated in 1108 schizophrenic patients (64.4% smokers) and 1584 controls (31.1% smokers). PRSs for smoking initiation, educational attainment, body mass index and age at first birth were associated with smoking in patients and controls, explaining a similar percentage of variance in both groups. Attention\u2010deficit hyperactivity disorder (ADHD) PRS was associated with smoking only in schizophrenia. This association remained significant after adjustment by psychiatric cross\u2010disorder PRS. A PRS combining all the traits was more explanative than smoking initiation PRS alone, indicating that genetic susceptibility to the other traits plays an additional role in smoking behaviour. Smoking initiation PRS was also associated with schizophrenia in the whole sample, but the significance was lost after adjustment for smoking status. This same pattern was observed in the analysis of specific SNPs at the <jats:italic>CHRNA5\u2013CHRNA3\u2013CHRNB4<\/jats:italic> cluster associated with both traits. Overall, the results indicate that the same genetic factors are involved in smoking susceptibility in schizophrenia and in general population and are compatible with smoking acting, directly or indirectly, as a risk factor for schizophrenia that contributes to the high prevalence of smoking in these patients. The contrasting results for ADHD PRS may be related to higher ADHD symptomatology in schizophrenic patients.<\/jats:p>","DOI":"10.1111\/adb.13104","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T06:52:09Z","timestamp":1636959129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A polygenic approach to the association between smoking and schizophrenia"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-1636","authenticated-orcid":false,"given":"Laila","family":"Al\u2010Soufi","sequence":"first","affiliation":[{"name":"Psychiatric Genetics Group Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Department of Zoology, Genetics and Physical Anthropology Universidade de Santiago de Compostela (USC)  Santiago de Compostela 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