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The objective was to further investigate in a natural setting influential risk factors associated with clinically significant weight gain. An observational follow-up study was conducted. Patients when initiating treatment with whatever antipsychotic were included; a structured questionnaire was applied at baseline, 3 and 6\u00a0months later; a blood sample was obtained. In a nested case\u2013control approach, patients with an increase\u2009\u2265\u20097% of their initial weight were considered as cases, the remaining, as controls. The results showed that, out of 185 patients, 137 completed the 6-month follow-up (cases, 38; controls, 99). Weight gain gradually and significantly increased in cases (baseline, 65.0\u00a0kg; 6\u00a0months, 74.0\u00a0kg) but not in controls (65.6\u00a0kg and 65.8\u00a0kg, respectively). Age (adjusted OR\u2009=\u20090.97, 95% CI\u2009=\u20090.96\u20130.99, <jats:italic>p<\/jats:italic>\u2009=\u20090.004), olanzapine (adjusted OR\u2009=\u20092.98, 95% CI\u2009=\u20091.13\u20137.80, <jats:italic>p<\/jats:italic>\u2009=\u20090.027) and quetiapine (adjusted OR\u2009=\u20090.25, 95%\u2009=\u20090.07\u20130.92, <jats:italic>p<\/jats:italic>\u2009=\u20090.037) significantly associated with weight gain. An association was also found for the <jats:italic>CNR1<\/jats:italic> (rs1049353) and <jats:italic>INSIG2<\/jats:italic> (rs7566605) polymorphisms. In conclusion, an increased risk of antipsychotics-induced weight gain was observed for younger age and olanzapine, and a relative lower risk for quetiapine. A potential role of <jats:italic>CNR1<\/jats:italic> rs1049353 and <jats:italic>INSIG2<\/jats:italic> rs7566605 polymorphisms is suggested.<\/jats:p>","DOI":"10.1038\/s41598-021-94700-9","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T10:02:50Z","timestamp":1627380170000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case\u2013control study"],"prefix":"10.1038","volume":"11","author":[{"given":"Natalia","family":"Jimeno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Velasco-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Fierro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Duran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Carvajal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"94700_CR1","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1056\/NEJMoa051688","volume":"353","author":"JA Lieberman","year":"2005","unstructured":"Lieberman, J. 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