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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/156048
Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
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In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. 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 'in silico' 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 = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). 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.
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BOLOC, Daniel, et al. Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics. Translational Psychiatry. 2018. Vol. 8, num. 1, pags. 276. ISSN 2158-3188. [consulted: 7 of June of 2026]. Available at: https://hdl.handle.net/2445/156048