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The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality \u201cin silico\u201d of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009131) and replicate it in two independent cohorts (Replication Cohort 1,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009113; Replication Cohort 2,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.\n                  <\/jats:p>","DOI":"10.1038\/s41398-018-0330-4","type":"journal-article","created":{"date-parts":[[2018,12,13]],"date-time":"2018-12-13T10:36:50Z","timestamp":1544697410000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipsychotics"],"prefix":"10.1038","volume":"8","author":[{"given":"Daniel","family":"Boloc","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gortat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Qi","family":"Cheng-Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Garc\u00eda-Cerro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Parellada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeronimo","family":"Saiz-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolo J.","family":"Cuesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Gass\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Lafuente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquel","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-6298","authenticated-orcid":false,"given":"Sergi","family":"Mas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,13]]},"reference":[{"key":"330_CR1","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1176\/appi.ajp.161.4.692","volume":"161","author":"TP Gilmer","year":"2004","unstructured":"Gilmer, T. 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This study was supported by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS, Fondo de Investigacion Sanitaria PI13\/00812, PI16\/0122) and FEDER-Uni\u00f3n Europea.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.S.-R. has been a speaker for and on the advisory boards of Lilly, GlaxoSmithKline, Lundbeck, Janssen, Servier, and Pfizer and has received grant\/honoraria from Lilly and Astra-Zeneca. M.B. has been a consultant for, received grant\/research support and honoraria from, and been on the speakers\/advisory board of ABBiotics, Adamed, Almirall, AMGEN, Boehringer, Eli Lilly, Ferrer, Forum Pharmaceuticals, Gedeon, Hersill, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Roche and Servier. The other authors declare no conflict of interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"276"}}