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Identifying key transcription factors for pharmacogenetic studies of antipsychotics induced extrapyramidal symptoms

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Abstract

Introduction

We explore the transcription factors involved in the molecular mechanism of antipsychotic (AP)-induced acute extrapyramidalsymptoms (EPS) in order to identify new candidate genes for pharmacogenetic studies.

Methods

Protein-protein interaction (PPI) networks previously created from three pharmacogenomic models (in vitro, animal, and peripheral blood inhumans) were used to, by means of several bioinformatic tools; identify key transcription factors (TFs) that regulate each network. Once the TFs wereidentified, SNPs disrupting the binding sites (TFBS) of these TFs in the genes of each network were selected for genotyping. Finally, SNP-basedassociations with EPS were analyzed in a sample of 356 psychiatric patients receiving AP.

Results

Our analysis identified 33 TFs expressed in the striatum, and 125 SNPs disrupting TFBS in 50 genes of our initial networks. Two SNPs (rs938112,rs2987902) in two genes (LSMAP and ABL1) were significantly associated with AP induced EPS (p < 0.001). These SNPs disrupt TFBS regulated byPOU2F1.

Conclusion

Our results highlight the possible role of the disruption of TFBS by SNPs in the pharmacological response to AP.

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References

  • Aberg K, Adkins DE, Bukszár J, Webb BT, Caroff SN, Miller DD et al (2010) Genome wide association study of movement-related adverse antipsychotic effects. Biol Psychiatry 67:279–282

    Article  PubMed  CAS  Google Scholar 

  • Al Hadithy AF, Wilffert B, Bruggeman R, Stewart RE, Brouwers JR, Matroos GE et al (2009) Lack of association between antipsychotic-induced parkinsonism or its subsymptoms and rs4606 SNP of RGS2 gene in African-Caribbeans and the possible role of the medication: the Curacao extrapyramidal syndromes study X. Hum Psychopharmacol 24:123–128

    Article  PubMed  CAS  Google Scholar 

  • Alkelai A, Greenbaum L, Rigbi A, Kanyas K, Lerer B (2009) Genome-wide association study of antipsychotic-induced parkinsonism severity among schizophrenia patients. Psychopharmacology 206:491–499

    Article  CAS  PubMed  Google Scholar 

  • Ansari KI, Ogawa D, Rooj AK, Lawler SE, Krichevsky AM, Johnson MD, Chiocca EA, Bronisz A, Godlewski J (2015) Glucose-based regulation of miR-451/AMPK signaling depends on the OCT1 transcription factor. Cell Rep 11:902–909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernardo M, Bioque M, Parellada M, Saiz Ruiz J, Cuesta MJ, Llerena A, Sanjuán J, Castro-Fornieles J, Arango C, Cabrera B, PEPs Group (2013) Assessing clinical and functional outcomes in a gene-environment interaction study in first episode of psychosis (PEPs). Rev Psiquiatr Salud Ment 6:4–16

    Article  PubMed  Google Scholar 

  • Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, Fienberg AA, Tsai LH, Kwon YT, Girault JA, Czernik AJ, Huganir RL, Hemmings HC Jr, Nairn AC, Greengard P (1999) Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 402:669–671

    Article  CAS  PubMed  Google Scholar 

  • Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z, Galon J (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blake JA, Eppig JT, Kadin JA, Richardson JE, Smith CL, Bult CJ (2017) the Mouse Genome Database Group,. Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse. Nucleic Acids Res 45:D723–D729

    Article  CAS  PubMed  Google Scholar 

  • Crowley JJ, Kim Y, Szatkiewicz JP, Pratt AL, Quackenbush CR, Adkins DE, van den Oord E, Bogue MA, Yang H, Wang W, Threadgill DW, de Villena FPM, McLeod HL, Sullivan PF (2012) Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice. Mamm Genome 23:322–335

    Article  CAS  PubMed  Google Scholar 

  • Dalvai M, Schubart K, Besson A, Matthias P (2010) Oct1 is required for mTOR-induced G1 cell cycle arrest via the control of p27(Kip1) expression. Cell Cycle 99:3933–3944

    Article  CAS  Google Scholar 

  • Divac N, Prostran M, Jakovcevski I, Cerovac N (2014) Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int 656370

  • Dolzan V, Plesnicar BK, Serreti A, Mandelli L, Zalar B, Koprivsek J et al (2007) Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment. Am J Med Genet B Neuropsychiatr Genet 144B:809–815

    Article  CAS  PubMed  Google Scholar 

  • Drago A, Crisafulli C, Serretti A (2011) The genetics of antipsychotic induced tremors: a genome-wide pathway analysis on the STEP-BD SCP sample. Am J Med Genet B Neuropsychiatr Genet 156B:975–986

    Article  PubMed  CAS  Google Scholar 

  • Drago A, Giegling I, Schäfer M, Hartmann AM, Möller HJ, De Ronchi D et al (2012) No association of a set of candidate genes on haloperidol side effects. PLoS One 7:e44853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drago A, Giegling I, Schäfer M, Hartmann AM, Friedl M, Konte B, Möller HJ, de Ronchi D, Stassen HH, Serretti A, Rujescu D (2013) AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment. Eur Neuropsychopharmacol 23:887–894

    Article  CAS  PubMed  Google Scholar 

  • Gassó P, Mas S, Bernardo M, Alvarez S, Parellada E, Lafuente A (2009) A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharm J 9:404–410

    Google Scholar 

  • Giegling I, Drago A, Dolzan V, Plesnicar BK, Schafer M, Hartmann AM et al (2011) Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. Pharmacogenet Genomics 21:206–216

    Article  CAS  PubMed  Google Scholar 

  • González JR, Armengol L, Solé X, Guinó E, Mercader JM, Estivill X, Moreno V (2007) SNPassoc: an R package to perform whole genome association studies. Bioinformatics 23:644–645

    PubMed  Google Scholar 

  • Greenbaum L, Strous RD, Kanyas K, Merbl Y, Horowitz A, Karni O, Katz E, Kotler M, Olender T, Deshpande SN, Lancet D, Ben-Asher E, Lerer B (2007) Association of the RGS2 gene with extrapyramidal symptoms induced by treatment with antipsychotic medication. Pharmacogenet Genomics 17:519–528

    Article  CAS  PubMed  Google Scholar 

  • Gunes A, Scordo MG, Jaanson P, Dahl ML (2007) Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients. Psychopharmacology (Berlin) 190:479–484

    Article  CAS  Google Scholar 

  • Gunes A, Dahl ML, Spina E, Scordo MG (2008) Further evidence for the association between 5-HT2C receptor gene polymorphisms and extrapyramidal side effects in male schizophrenic patients. Eur J Clin Pharmacol 64:477–482

    Article  CAS  PubMed  Google Scholar 

  • Güzey C, Scordo MG, Spina E, Landsem VM, Spigset O (2007) Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms. Eur J Clin Pharmacol 63:233–241

    Article  PubMed  CAS  Google Scholar 

  • Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SGN, Jones AR (2012) An anatomically comprehensive atlas of the adult human transcriptome. Nature 489:391–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heinla I, Leidmaa E, Kongi K, Pennert A, Innos J, Nurk K et al (2015) Gene expression patterns and environmental enrichment-induced effects in the hippocampi of mice suggest importance of Lsamp in plasticity. Front Neurosci 9:205

    Article  PubMed  PubMed Central  Google Scholar 

  • Kang J, Shakya A, Tantin D (2009) Stem cells, stress, metabolism and cancer: a drama in two Octs. Trends Biochem Sci 34:491–499

    Article  CAS  PubMed  Google Scholar 

  • Kapur S, Remington G (2001) Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biol Psychiatry 50:873–883

    Article  CAS  PubMed  Google Scholar 

  • Karolchik D, Hinrichs AS, Furey TS, Roskin KM, Sugnet CW, Haussler D, Kent WJ (2004) The UCSC Table browser data retrieval tool. Nucleic Acids Res 32:D493–D496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koido K, Traks T, Balõtšev R, Eller T, Must A, Koks S, Maron E, Tõru I, Shlik J, Vasar V, Vasar E (2012) Associations between LSAMP gene polymorphisms and major depressive disorder and panic disorder. Transl Psychiatry 2:e152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koido K, Janno S, Traks T, Parksepp M, Ljubajev Ü, Veiksaar P, Must A, Shlik J, Vasar V, Vasar E (2014) Associations between polymorphisms of LSAMP gene and schizophrenia. Psychiatry Res 215:797–798

    Article  CAS  PubMed  Google Scholar 

  • Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gassó P et al (2007) Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr Res 90:115–122

    Article  PubMed  Google Scholar 

  • Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gassó P et al (2008) Polymorphism of dopamine D2 receptor (TaqIA, TaqIB, and-141C Ins/Del) and dopamine degradation enzyme (COMT G158A, A-278G) genes and extrapyramidal symptoms in patients with schizophrenia and bipolar disorders. Psychiatry Res 161:131–141

    Article  CAS  PubMed  Google Scholar 

  • Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9:559

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lawford BR, Barnes M, Swagell CD, Connor JP, Burton SC, Heslop K, Voisey J, Morris CP, Nyst P, Noble EP, Young RM (2013) DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia. J Psychopharmacol 27:343–348

    Article  CAS  PubMed  Google Scholar 

  • Mas S, Gassó P, Alvarez S, Parellada E, Bernardo M, Lafuente A (2012) Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6, CYP3A5 and ABCB1 genotypes. Pharm J 12:255–259

    CAS  Google Scholar 

  • Mas S, Gassó P, Bernardo M, Lafuente A (2013) Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies. Eur Neuropsychopharmacol 23:329–337

    Article  CAS  PubMed  Google Scholar 

  • Mas S, Gassó P, Parellada E, Bernardo M, Lafuente A (2015a) Network analysis of gene expression in peripheral blood identifies mTOR and NF-κB pathways involved in antipsychotic-induced extrapyramidal symptoms. Pharm J 15:452–460

    CAS  Google Scholar 

  • Mas S, Gassó P, Lafuente A (2015b) Applicability of gene expression and systems biology to develop pharmacogenetic predictors; antipsychotic-induced extrapyramidal symptoms as an example. Pharmacogenomics 16:1975–1988

    Article  CAS  PubMed  Google Scholar 

  • Mas S, Gassó P, Ritter MA, Malagelada C, Bernardo M, Lafuente A (2015c) Pharmacogenetic predictor of extrapyramidal symptoms induced by antipsychotics: multilocus interaction in the mTOR pathway. Eur Neuropsychopharmacol 25:51–59

    Article  CAS  PubMed  Google Scholar 

  • Mas S, Gassó P, Boloc D, Rodriguez N, Mármol F, Sánchez J, Bernardo M, Lafuente A (2016a) Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms. Pharm J 16:293–300

    CAS  Google Scholar 

  • Mas S, Gassó P, Lafuente A, Bioque M, Lobo A, Gonzàlez-Pinto A et al (2016b) Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes. Pharm J 16:439–445

    CAS  Google Scholar 

  • McClay JL, Adkins DE, Aberg K, Stroup S, Perkins DO, Vladimirov VI et al (2011) Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics. Mol Psychiatry 16:76–85

    Article  CAS  PubMed  Google Scholar 

  • Minguez P, Götz S, Montaner D, Al-Shahrour F, Dopazo J (2009) SNOW, a web-based tool for the statistical analysis of protein-protein interaction networks. Nucleic Acids Res 37:W109–W114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishi A, Bibb JA, Snyder GL, Higashi H, Nairn AC, Greengard P (2000) Amplification of dopaminergic signaling by a positive feedback loop. Proc Natl Acad Sci U S A 97:12840–12845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nurnberger JI Jr, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I (2014) Identification of pathways for bipolar disorder: a meta-analysis. JAMA Psychiatry 71(6):657–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pance A (2016) Oct-1, to go or not to go? That is the PolII question. Biochim Biophys Acta 1859:820–824

    Article  CAS  PubMed  Google Scholar 

  • Philips MA, Lilleväli K, Heinla I, Luuk H, Hundahl CA, Kongi K, Vanaveski T, Tekko T, Innos J, Vasar E (2015) Lsamp is implicated in the regulation of emotional and social behavior by use of alternative promoters in the brain. Brain Struct Funct 220:1381–1393

    Article  PubMed  Google Scholar 

  • Roussos P, Mitchell AC, Voloudakis G, Fullard JF, Pothula VM, Tsang J, Stahl EA, Georgakopoulos A, Ruderfer DM, Charney A, Okada Y, Siminovitch KA, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Plenge RM, Raychaudhuri S, Fromer M, Purcell SM, Brennand KJ, Robakis NK, Schadt EE, Akbarian S, Sklar P (2014) A role for noncoding variation in schizophrenia. Cell Rep 9:1417–1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schork AJ, Thompson WK, Pham P, Torkamani A, Roddey JC, Sullivan PF, Kelsoe JR, O'Donovan MC, Furberg H, The Tobacco and Genetics Consortium, The Bipolar Disorder Psychiatric Genomics Consortium, The Schizophrenia Psychiatric Genomics Consortium, Schork NJ, Andreassen OA, Dale AM (2013) All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs. PLoS Genet 9:e1003449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simpson GM, Angus JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 212:11–19

    Article  CAS  PubMed  Google Scholar 

  • Sokolowski M, Wasserman J, Wasserman D (2016) Polygenic associations of neurodevelopmental genes in suicide attempt. Mol Psychiatry 21:1381–1390

    Article  CAS  PubMed  Google Scholar 

  • Strand AD, Baquet ZC, Aragaki AK, Holamans P, Yang L, Cleren C et al (2007) Expression profiling of Huntington’s disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci 27:11758–11768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan PF, Fan C, Perou CM (2006) Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 141B:261–268

    Article  PubMed  Google Scholar 

  • The 1000 Genomes Project Consortium (2015) A global reference for human genetic variation. Nature 526:68–74

    Article  CAS  Google Scholar 

  • Tybura P, Trześniowska-Drukała B, Bienkowski P, Beszlej A, Frydecka D, Mierzejewski P, Samochowiec A, Grzywacz A, Samochowiec J (2014) Pharmacogenetics of adverse events in schizophrenia treatment: comparison study of ziprasidone, olanzapine and perazine. Psychiatry Res 219:261–267

  • Vanaveski T, Singh K, Narvik J, Eskla KL, Visnapuu T, Heinla I et al (2017) Promoter-specific expression and genomic structure of IgLON family genes in mouse. Front Neurosci 11:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Weiden PJ (2007) Switching antipsychotics as a treatment strategy for antipsychotic-induced weight gain and dyslipidemia. J Clin Psychiatry 68:34–39

    PubMed  Google Scholar 

  • Wilffert B, Al Hadithy AF, Sing VJ, Matroos G, Hoeck HW, van Os J et al (2009) The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX. J Psychopharmacol 23:652–659

    Article  CAS  PubMed  Google Scholar 

  • Zhou ZH, Wu YF, Wang XM, Han YZ (2017) The c-Abl inhibitor in Parkinson disease. Neurol Sci 38:547–552

    Article  PubMed  Google Scholar 

  • Zivković M, Mihaljevic-Peles A, Bozina N, Sagud M, Nikolac-Perkovic M, Vuksan-Cusa B et al (2013) The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol. J Clin Psychopharmacol 33:593–599

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank the Language Advisory Service of the University of Barcelona, Spain, for manuscript revision. The authors also thank all subjects and their families for the time and effort spent on this study.

Funding

This study was supported by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS, Fondo de Investigacion Sanitaria PI10/02430, PI13/00812, PI16/0122) and the Catalan Innovation, Universities and Enterprise Authority (Grants DURSI 2014SGR436 and 2014SGR441). DB is supported by a FPU fellowship (FPU14/06834) from the “Ministerio de Educación, Cultura y Deporte.”

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Authors and Affiliations

  1. Department of Medicine, University of Barcelona, Barcelona, Spain

    Daniel Boloc & Miquel Bernardo

  2. Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain

    Natalia Rodríguez

  3. Dept. Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain

    Teresa Torres, Susana García-Cerro, Patricia Gassó, Amalia Lafuente, Sergi Mas & Joan Albert Arnaiz

  4. Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain

    Mara Parellada

  5. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Madrid, Spain

    Mara Parellada, Jeronimo Saiz-Ruiz, Manuel J. Cuesta, Miquel Bernardo, Amalia Lafuente & Sergi Mas

  6. Hospital Ramon y Cajal, Universidad de Alcala, IRYCIS, Madrid, Spain

    Jeronimo Saiz-Ruiz

  7. Department of Psychiatry, Complejo Hospitalario de Navarra. Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain

    Manuel J. Cuesta

  8. Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain

    Miquel Bernardo

  9. Spain The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain

    Miquel Bernardo, Patricia Gassó, Amalia Lafuente & Sergi Mas

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  1. Daniel Boloc
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  2. Natalia Rodríguez
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  3. Teresa Torres
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  9. Patricia Gassó
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  10. Amalia Lafuente
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Correspondence to Sergi Mas or Joan Albert Arnaiz.

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Conflict of interest

J. Saiz-Ruiz 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. Bernardo 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.

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Boloc, D., Rodríguez, N., Torres, T. et al. Identifying key transcription factors for pharmacogenetic studies of antipsychotics induced extrapyramidal symptoms. Psychopharmacology 237, 2151–2159 (2020). https://doi.org/10.1007/s00213-020-05526-8

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