ArticlePloS one2014
Pathway analyses implicate glial cells in schizophrenia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism.Journal of human genetics · 2017Pooled it
- The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study.Scientific reports · 2021Trial
- IncreasingBiological psychiatry global open science · 2025Article
- Repurposing medications to prevent psychosis.Npj mental health research · 2025Review
- An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth.Schizophrenia research · 2022Article
- Validating methods for testing natural molecules on molecular pathways of interest in silico and in vitro.Journal of preventive medicine and hygiene · 2022Article
- Synaptic processes and immune-related pathways implicated in Tourette syndrome.Translational psychiatry · 2021Article
- Cortical cellular diversity and development in schizophrenia.Molecular psychiatry · 2021Review
- Intracellular Signaling Cascades in Bipolar Disorder.Current topics in behavioral neurosciences · 2021Review
- iPSC-derived homogeneous populations of developing schizophrenia cortical interneurons have compromised mitochondrial function.Molecular psychiatry · 2020Article
- The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder.NPJ genomic medicine · 2020Article
- Review
- Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.Molecular psychiatry · 2019Article
- An Overview of Animal Models Related to Schizophrenia.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2019Review
- Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems.NPJ schizophrenia · 2018Review
- Oligodendrocyte differentiation of induced pluripotent stem cells derived from subjects with schizophrenias implicate abnormalities in development.Translational psychiatry · 2018Article
- Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance: a genome-wide genetic interaction study.Molecular medicine (Cambridge, Mass.) · 2018Article
- The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia.European psychiatry : the journal of the Association of European Psychiatrists · 2018Review
- Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis ofFrontiers in psychiatry · 2018Article
- Oligodendroglia-lineage cells in brain plasticity, homeostasis and psychiatric disorders.Current opinion in neurobiology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge.
methodTen publically available gene sets (pathways) related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bipolar disorder using MAGENTA as the primary analysis method. To determine the robustness of associations, secondary analyses were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric Genomics Consortium (PGC) were used for all analyses. There were 1,068,286 SNP-level p-values for schizophrenia (9,394 cases/12,462 controls), and 2,088,878 SNP-level p-values for bipolar disorder (7,481 cases/9,250 controls).
resultsThe Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75% requirement for individual gene significance) and also achieved nominal levels of significance with INRICH (p = 0.0057) and ALIGATOR (p = 0.022). For bipolar disorder, Set Screen yielded nominally and method-wide significant associations to all three glial pathways, with strongest association to the Glia-Astrocyte pathway (p = 0.002).
conclusionsConsistent with findings of white matter abnormalities in schizophrenia by other methods of study, the Glia-Oligodendrocyte pathway was associated with schizophrenia in our genomic study. These findings suggest that the abnormalities of myelination observed in schizophrenia are at least in part due to inherited factors, contrasted with the alternative of purely environmental causes (e.g. medication effects or lifestyle). While not the primary purpose of our study, our results also highlight the consequential nature of alternative choices regarding pathway analysis, in that results varied somewhat across methods, despite application to identical datasets and pathways.
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