ArticleJAMA psychiatry2022
Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia.
Article in JAMA psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 5 of them syntheses that pooled it.
What it found
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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
62 citing papers in PubMed, 5 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Brain structural abnormalities in treatment-resistant schizophrenia.Molecular psychiatry · 2026Pooled it
- A multi-cohort assessment of the polygenic prediction in ADHD treatment response.Psychiatry research · 2026Pooled it
- Genome-wide association meta-analysis and rare copy number variant analysis of treatment-resistant depression.Molecular psychiatry · 2025Pooled it
- Pharmacogenomic scores in psychiatry: systematic review of current evidence.Translational psychiatry · 2024Pooled it
- Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review.CNS drugs · 2022Pooled it
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- The association of schizophrenia polygenic scores with continuously-hospitalized, treatment-resistant schizophrenia.Molecular psychiatry · 2026Article
- Genetic overlap between treatment-resistant schizophrenia and smoking initiation.The international journal of neuropsychopharmacology · 2026Article
- Splitting schizophrenia: divergent cognitive and educational outcomes revealed by genomic structural equation modelling.Molecular psychiatry · 2026Article
- Can Psychiatric Genetics Advance Without Incorporating a Life Course Perspective?Biological psychiatry · 2026Review
- Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal.Biological psychiatry · 2026Review
- Genetic evidence for causal relationship between general cognition and treatment resistance in schizophrenia.Translational psychiatry · 2026Article
- A clinical control study of modified electroconvulsive therapy and sodium valproate as enhancement strategies for ultra-treatment-resistant schizophrenia.Schizophrenia research. Cognition · 2026Article
- UntargetedTranslational psychiatry · 2026Article
- Genetics to Improve Outcomes in Schizophrenia (GENios): A within-case molecular genetic study protocol.PloS one · 2026Article
- A scoping review of genetic studies of treatment-resistant schizophrenia.Frontiers in genetics · 2026Review
- The impact of collider bias on genetic prediction in psychotic disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Genomics of schizophrenia, bipolar disorder and major depressive disorder.Nature reviews. Genetics · 2025Review
- Association of astrocyte-specific gene expression in the dorsolateral prefrontal cortex with clozapine treatment in schizophrenia.Translational psychiatry · 2025Article
- Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First Episode Study.Schizophrenia bulletin · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
71 authors at 20 institutions in 16 countries.
Funding
Abstract
importanceAbout 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.
objectiveTo examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. DESIGN, SETTING, AND
participantsTwo case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). MAIN OUTCOMES AND MEASURES: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.
resultsThe study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04). CONCLUSIONS AND RELEVANCE: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.
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