ArticleTranslational psychiatry2022
Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.
Open access · goldAbstract readMulticenter Study
In one paragraph
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
4.3field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Meta-analyses of clozapine, norclozapine levels and their ratio across three genome wide association studies.Translational psychiatry · 2025Pooled it
- Pharmacogenomic scores in psychiatry: systematic review of current evidence.Translational psychiatry · 2024Pooled it
- Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.Translational psychiatry · 2024Pooled it
- Negative symptomatology and clozapine-induced obsessive-compulsive symptoms: a cross-sectional analysis.European archives of psychiatry and clinical neuroscience · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- A scoping review of genetic studies of treatment-resistant schizophrenia.Frontiers in genetics · 2026Review
- Transcription factors of the Nuclear Factor I (NFI) family control hepatocyte differentiation and cytochrome P450 activity in human liver.Pharmacological research · 2025Article
- Determinants of patient satisfaction in clozapine users: results from the Clozapine International Consortium (CLOZIN).Schizophrenia (Heidelberg, Germany) · 2025Article
- Transdiagnostic Effects of Schizophrenia Polygenic Scores on Treatment Outcomes in Major Psychiatric Disorders.Neuropsychiatric disease and treatment · 2025Review
- UnidentifiedJournal of psychopharmacology (Oxford, England) · 2024Article
- Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.European archives of psychiatry and clinical neuroscience · 2024Article
- Biomarker Methodologies: A NIMH Perspective.Advances in neurobiology · 2024Review
- Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.medRxiv : the preprint server for health sciences · 2023Article
- The emergence, implementation, and future growth of pharmacogenomics in psychiatry: a narrative review.Psychological medicine · 2023Review
- Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders: The Functional Role of CYP2D6 and CYP2C19.Journal of personalized medicine · 2023Article
- The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions.Psychiatry and clinical psychopharmacology · 2023Article
- Article
- Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia.JAMA psychiatry · 2023Observational
Corrections and comments
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Authors and funding
49 authors at 20 institutions in 10 countries.
C Okhuijsen-Pfeifer *Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-9649-3879
M Z van der Horst *Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0001-5090-4137
C A Bousman *Department of Medical Genetics, University of Calgary, Calgary, Canada.ORCID http://orcid.org/0000-0001-6303-8696
B Lin *Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center, Utrecht, The Netherlands.
K R van EijkDepartment of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Brain Center, Utrecht, The Netherlands.
S RipkeCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Berlin, Germany.
Y AyhanDepartment of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
M O BabaogluDepartment of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
M BakDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.
W AlinkMulticomplexe Zorg, Pro Persona, Wolfheze, The Netherlands.
H van BeekClinical Recovery Clinic, Mental Health Services Rivierduinen, Leiden, The Netherlands.
E BeldMental Health Organization North-Holland North location Den Helder, Den Helder, The Netherlands.
A BouhuisProgram for early psychosis & severe mental illness, Pro Persona Mental Healthcare, Wolfheze, The Netherlands.
M EdlingerDepartment of Psychiatry, Psychotherapy and Psychosomatics, Division for Psychiatry I, Medical University Innsbruck, Innsbruck, Austria.
I M ErdoganDepartment of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.ORCID http://orcid.org/0000-0003-3319-4924
A ErtuğrulDepartment of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
G YocaDepartment of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
I P EverallDepartment of Psychiatry, University of Melbourne, Melbourne Neuropsychiatry Centre, Melbourne, Australia.
T GörlitzDepartment of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
GROUP (Genetic Risk and Outcome of Psychosis) investigators
K P GrootensReinier van Arkel, s-Hertogenbosch, The Netherlands.
S GutwinskiCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Berlin, Germany.
T HallikainenDepartment of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland.
E Jeger-LandArkin, Institute for Mental Health, Amsterdam, The Netherlands.
M de KoningArkin, Institute for Mental Health, Amsterdam, The Netherlands.
M LähteenvuoDepartment of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland.ORCID http://orcid.org/0000-0002-7244-145X
S E LeggeDivision of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.ORCID http://orcid.org/0000-0001-6617-0289
S LeuchtDepartment of Psychiatry and Psychotherapy, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
C MorgenrothCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Berlin, Germany.
A MüderrisoğluDepartment of Pharmacology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey.
A NarangDepartment of Medical Genetics, University of Calgary, Calgary, Canada.
C PantelisDepartment of Psychiatry, University of Melbourne, Melbourne Neuropsychiatry Centre, Melbourne, Australia.ORCID http://orcid.org/0000-0002-9565-0238
A F PardiñasDivision of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.ORCID http://orcid.org/0000-0001-6845-7590
T Oviedo-SalcedoDepartment of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
J Schneider-ThomaDepartment of Psychiatry and Psychotherapy, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
S SchreiterCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Berlin, Germany.
E Repo-TiihonenDepartment of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland.
H TuppurainenDepartment of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland.
M VeereschildGGNet Mental Health, Warnsveld, The Netherlands.
S VeermanMental Health Organization North-Holland North location Alkmaar, Alkmaar, The Netherlands.
M de VosGGNet Mental Health, Warnsveld, The Netherlands.
E WagnerDepartment of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-7147-6167
D CohenMental Health Organization North-Holland North location Heerhugowaard, Heerhugowaard, The Netherlands.
J P A M BogersHigh Care Clinics, Mental Health Services Rivierduinen, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-7273-0027
J T R WaltersDivision of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
A E Anil YağcıoğluDepartment of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
J TiihonenDepartment of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland.ORCID http://orcid.org/0000-0002-0400-6798
A HasanDepartment of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
J J LuykxDepartment of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center, Utrecht, The Netherlands. j.luykx@umcutrecht.nl.ORCID http://orcid.org/0000-0002-6439-2774
Niuvanniemi Hospital · FIUtrecht University · NLHacettepe University · TRLMU Klinikum · DEMaastricht University · NLThe University of Melbourne · AUTUM Klinikum · DEGGNet · NLGGZ Rivierduinen · NLHumboldt-Universität zu Berlin · DEPro Persona · NLUniversity Medical Center Groningen · NLUniversity Medical Center Utrecht · NLUniversity of Groningen · NLArkin · NLGeriant · NLHewlett-Packard (Netherlands) · NLInnsbruck Medical University · ATRadboud University Nijmegen · NLReinier van Arkel · NL
Funding
Medical Research Council MR/L010305/1
Abstract
Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10
Indexed as
Antipsychotic AgentsClozapineCytochrome P-450 CYP2C19SchizophreniaCytochrome P-450 CYP1A2Cytochrome P-450 CYP2D6Genome-Wide Association StudyHumansAntipsychotic AgentsClozapineCYP2C19 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP2D6
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